Feasibility and preliminary efficacy of behavioral activation for treatment of depression in autistic adolescents.

LAY ABSTRACT: Depression is common among autistic youth and has a significant negative impact on quality of life and day-to-day functioning. Despite great need for efficacious treatments, there are currently limited research-supported interventions for depression symptoms in autistic young people. This study tested a novel, behavior-based approach or psychotherapy for treatment of depression symptoms in autistic adolescents without intellectual disability (i.e. Behavioral Activation for Autistic Adolescents, BA-A) with 15 youth (11-16 years old). BA-A is an individually delivered 12-session therapy that was developed for and to meet the needs of autistic youth with depression. Results found that autistic youth and their caregivers were able to participate in BA-A therapy sessions, and clinicians were able to deliver BA-A in accordance with the treatment manual. Notably, results demonstrated that autistic youth depression symptoms significantly improved after participating in BA-A. Furthermore, anxiety symptoms and social skills significantly improved following BA-A.

Impact of adverse childhood experiences and family resilience on sleep duration in autistic children.

LAY ABSTRACT: Autistic children are more likely to have sleep difficulties and to experience adverse childhood experiences. Adverse childhood experiences can include parental divorce, bullying, or witnessing violence. We also know that children in families who are resilient (e.g. families who are connected, work together, and help each other) are less impacted by adverse childhood experiences. Our study examined whether there was a relationship between adverse childhood experiences and sleep duration in autistic children. We also wanted to find out whether family resilience protects from the negative impact of adverse childhood experiences on sleep duration. We used data from 3247 parent surveys about their children that we got from the National Survey of Children's Health. We found that children with adverse childhood experiences are more likely to get less sleep. We also found that children with resilient families were more likely to get more sleep. Our results show that family resilience helps weaken the relationship between adverse childhood experiences and sleep, so it is important to help families build resilience.

Incidence of drug-related adverse events related to the use of high-alert drugs: A systematic review of randomized controlled trials.

Background: High-alert medication (HAM) is more predictable to cause significant harm to the patient, even when used as intended. The damage related to the HAM lead not only suffering to the patient, but also raise the additional costs associated with care. Objective: Evaluate the incidence of drug-related adverse events related to the use of high-alert medications. Methods: It was conducted an active search for information through COCHRANE databases, LILACS, SciELO, SCOPUS, PubMed/MEDLINE and WEB OF SCIENCE. The search strategy included the following terms: "Patient safety", "Medication errors" and "Hospital" and "High Alert Medications" or "Dangerous Drugs" in different combinations. Then two reviewers independently conducted a preliminary evaluation of relevant titles, abstracts and finally full-text. Studies quality was evaluated according to PRISMA declaration. Results: The systematic review evaluated seven articles, which showed that only 11 HAM identified in the literature could have serious events. The most frequently cited were warfarin (22.2%) which progressed from deep vein thrombosis to gangrene, suggesting lower initial doses, followed by cyclophosphamide (22.2%) and cyclosporine (22.2%) which presented invasive fungal infection and death. In addition to these, morphine was compared with its active metabolite (M6G), with M6G causing fewer serious clinical events related to nausea and vomiting, reducing the need for concomitant use of antiemetics. Conclusions: The most reported drug classes in the articles included that were related to incidence of drug-related adverse events in use of high-alert medications: morphine, M6G-glucuronide, haloperidol, promethazine, ivabradine, digoxin, warfarin, ximelagatran, cyclophosphamide, cyclosporine, and ATG. The formulate protocols for the use of these medications, with importance placed on evaluating, among the classes, the medication that causes the least harm.

Understanding autism diagnosis in primary care: Rates of diagnosis from 2004 to 2019 and child age at diagnosis.

LAY ABSTRACT: The current demand for autism diagnostic services exceeds the ability of the workforce to assess and diagnose children in a timely manner. One solution may be to equip primary care providers (PCPs) with the tools and expertise needed to diagnose autism within their practice. PCPs are often trusted professionals who have many touchpoints with children during early development, in which they can identify early signs of autism. Recent initiatives have focused on bolstering PCPs' diagnostic capabilities; however, no studies have examined how the rates of autism diagnosis in primary care have changed over time. We aimed to evaluate whether autism diagnosis in primary care has changed over time and how diagnosis in primary care relates to a child's age at the time of diagnosis. We found that the likelihood of a child being diagnosed by a PCP decreased by about 2% with every passing year from 2004 to 2019 when accounting for demographic characteristics. In our sample, PCPs diagnosed children approximately 1 year earlier than non-PCPs (e.g., psychologists and psychiatrists). Further research is needed to understand why the proportion of children diagnosed by PCPs decreases over time. However, this decrease suggests more work is needed to get capacity-building initiatives into community primary care practice. Though we must continue to find effective ways to build community PCPs' ability to diagnose autism, the present findings support the crucial role PCPs can play in early autism diagnosis.

Caregiver Perspectives Regarding Special Education Service Changes Amid COVID-19.

School instruction and service delivery changed dramatically amid disruptions caused by the COVID-19 pandemic. Children receiving special education services were especially vulnerable to the impact of reduced or eliminated school services as part of their Individualized Education Programs. Caregiver perspectives regarding the changes in school service delivery amid the pandemic were evaluated using qualitative methods. Caregivers reported reduced or eliminated services, inconsistencies in service delivery, challenges with distance learning, increased stress and advocacy efforts, and varying perceptions of student engagement and teacher efforts. The implications of school services changes are discussed.

Association Between Neighborhood Support and Family Resilience in Households with Autistic Children.

The capacity of families with autistic children to demonstrate resilience is a notable strength that has received little attention in the literature. A potential predictor of family resilience in households with autistic youth is neighborhood support. This study examined the relationship between neighborhood support and family resilience in households with autistic youth utilizing data from the National Survey of Children's Health. A structural equation model was constructed as neighborhood support and family resilience were latent variables. Findings demonstrated that neighborhood support significantly predicts family resilience. This study contributes to the literature as the first quantitative investigation of predictors of family resilience with this group. Strengths of autistic youth, their families, and their communities can be and should be leveraged to address challenges.

Friendship and Anxiety/Depression Symptoms in Boys With and Without Autism Spectrum Disorder.

The transition to adolescence may be a challenging time for individuals with autism spectrum disorder (ASD). This developmental period is marked by increased social demands and increasing anxiety and depression symptoms for many individuals with autism. As both of these factors may compound social difficulties and impact friendship experiences, this study explored the relations among autism symptom severity, internalizing symptoms, and friendship experiences in boys with and without ASD (with IQ > 75). Results showed that internalizing symptoms predicted quantity of close friendships in the ASD group. Given the observed relationship between internalizing symptoms and friendship experiences, social skills intervention programs should address possible internalizing symptoms associated with establishing/maintaining social relationships and perceived friendship quality.

A mixed methods study of autistic adults' mental health therapy experiences.

Autistic adults are at high risk for co-occurring mental health problems and need access to effective and appropriate mental health treatment. However, the relative effectiveness or acceptability of specific mental health strategies among autistic adults has not been previously examined. The current study sought to gain a deeper understanding of autistic adults' experiences and preferences regarding mental health strategies using a mixed methods approach. Autistic adults (n = 303, ages 21-77) completed online surveys and open-ended questions about their mental health and therapy experiences. Most (88.8%) had participated in therapy, with cognitive approaches being the most common. Regarding overall therapy experiences, qualitative analyses revealed four primary themes and nine subthemes. Therapist acceptance and understanding were seen as critical for therapy success, and many participants felt that therapy was helpful for personal growth. However, many participants found that talking in session was challenging and noted that aspects of the session format affected their ability to engage in therapy. Regarding specific strategies, four cross-cutting themes and eight strategy-specific subthemes were identified. A variety of strategies were seen as helpful for reducing anxiety and improving mood. However, autistic adults reported trouble generalizing strategies to daily life and found some techniques to be difficult to implement due, in part, to their unique autism-related needs. As the first study of its kind, the results underscore the importance of establishing a safe and accepting therapeutic relationship, providing accommodations to support communication needs, and considering individual differences and preferences when selecting mental health strategies for autistic clients.

Emergency Department Utilization Among Youth with Autism Spectrum Disorder: Exploring the Role of Preventive Care, Medical Home, and Mental Health Access.

The 2016-2018 National Surveys of Children's Health dataset was used to identify associations among preventive care, unmet health care needs, medical home access, and emergency department (ED) use among children and adolescents with autism spectrum disorder (ASD). Results indicated that youth with ASD had higher odds of using ED services if they had unmet mental health care needs (OR = 1.58, CI: 1.04-2.39) and lower odds of using ED services if they had access to a medical home (OR = 0.79, CI: 0.63-0.98). Findings suggest the importance of access to coordinated, comprehensive, and patient-centered care to address health care needs and prevent ED utilization among children and adolescents with ASD.

Unmet health care needs and health care quality in youth with autism spectrum disorder with and without intellectual disability.

LAY ABSTRACT: The increase in the prevalence of autism spectrum disorder has placed greater demands on the health care system. Children and adolescents with autism spectrum disorder often experience challenges accessing high-quality physical and mental health care due to characteristic social-communication deficits and behavioral difficulties, as well as high rates of complex medical and psychiatric comorbidities. Intellectual disability commonly co-occurs with autism spectrum disorder and individuals affected by this co-occurrence may have additional impairments that compound challenges accessing health care. This study investigated the relations among co-occurring intellectual disability, unmet physical and mental health care needs, and health care quality in a large, nationally distributed sample of youth with autism spectrum disorder using structural equation modeling techniques. Co-occurring intellectual disability was significantly associated with unmet mental health care needs in children with autism. In addition, unmet mental health care needs mediated the relationship between co-occurring intellectual disability and health care quality; youth with autism spectrum disorder and co-occurring intellectual disability who had a past-year unmet mental health need had significantly poorer caregiver-reported health care quality. These findings suggest that youth with autism spectrum disorder and co-occurring intellectual disability may be more likely to experience unmet mental health care needs and receive poorer quality of care than the broader autism spectrum disorder population.

Associations between domains of health-related quality of life and comorbid emotional and behavioral problems in youth with autism spectrum disorder.

BACKGROUND: Health-related quality of life (HRQoL) can be used as a measure of the impact of a particular disorder on one's daily functioning. Previous studies have found that comorbid psychiatric disorders in children and adolescents with autism spectrum disorder (ASD) are associated with poorer HRQoL than ASD alone. Less is known about potential associations between specific symptoms of comorbid psychopathology (i.e., emotional and behavioral problems) and domains of functioning or HRQoL in youth with ASD. METHOD: Participants were 470 children with ASD 2-14 years old recruited from one of three sites. Hierarchical multiple regressions were conducted with Pediatric Quality of Life Inventory 4.0 (PedsQL; Varni et al., 2001) HRQoL domains of physical functioning, emotional functioning, school functioning, and social functioning as the dependent variables. Covariates were entered at step 1, followed by the independent variables of interest at step 2: irritability, social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech. RESULTS: The study found that increased irritability was associated with poorer emotional and physical functioning and that greater social withdrawal was associated with worse social functioning. Furthermore, findings showed that more hyperactivity/noncompliance was associated with worse school functioning. CONCLUSIONS: Results demonstrated that certain emotional and behavioral symptoms are differentially associated with domains of HRQoL. This indicates that comorbid emotional and behavioral problems should be considered when measuring HRQoL in children with ASD. It also suggests that treating comorbid emotional/behavioral problems could improve HRQoL and functioning in certain domains for this population.

Primary Care Providers' Perceived Barriers and Needs for Support in Caring for Children with Autism.

A mixed methods approach was used to examine perspectives of 114 primary care providers regarding barriers and needs for support in caring for children with autism. The most common barriers related to lack of knowledge and resources for diagnosing and treating children with autism, and inadequate visit time and reimbursement.

A Comparison of Health Care Expenditures for Medicaid-Insured Children with Autism Spectrum Disorder and Asthma in an Expanding Accountable Care Organization.

As value-based care continues to expand, more children with autism spectrum disorder (ASD) will be treated by accountable care organizations (ACOs), provider organizations seeking to improve population health while reducing costs. To inform ACO strategies for children with ASD, this study compared health care expenditures of children insured by a Medicaid managed care organization, empaneled to a safety net ACO, with ASD, asthma, and neither diagnosis. Compared to other study groups, children with ASD were more costly, had lower rates of acute care, and had higher rates of "leaked" care provided by home- and community-based mental health agencies outside of the ACO. These findings highlight the need for unique value-based strategies for children with ASD in a public sector ACO.

Identification of suicidal behavior among psychiatrically hospitalized adolescents using natural language processing and machine learning of electronic health records.

OBJECTIVE: The rapid proliferation of machine learning research using electronic health records to classify healthcare outcomes offers an opportunity to address the pressing public health problem of adolescent suicidal behavior. We describe the development and evaluation of a machine learning algorithm using natural language processing of electronic health records to identify suicidal behavior among psychiatrically hospitalized adolescents. METHODS: Adolescents hospitalized on a psychiatric inpatient unit in a community health system in the northeastern United States were surveyed for history of suicide attempt in the past 12 months. A total of 73 respondents had electronic health records available prior to the index psychiatric admission. Unstructured clinical notes were downloaded from the year preceding the index inpatient admission. Natural language processing identified phrases from the notes associated with the suicide attempt outcome. We enriched this group of phrases with a clinically focused list of terms representing known risk and protective factors for suicide attempt in adolescents. We then applied the random forest machine learning algorithm to develop a classification model. The model performance was evaluated using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. RESULTS: The final model had a sensitivity of 0.83, specificity of 0.22, AUC of 0.68, a PPV of 0.42, NPV of 0.67, and an accuracy of 0.47. The terms mostly highly associated with suicide attempt clustered around terms related to suicide, family members, psychiatric disorders, and psychotropic medications. CONCLUSION: This analysis demonstrates modest success of a natural language processing and machine learning approach to identifying suicide attempt among a small sample of hospitalized adolescents in a psychiatric setting.

Preclinical profile of a dopamine D1 potentiator suggests therapeutic utility in neurological and psychiatric disorders.

DETQ, an allosteric potentiator of the dopamine D1 receptor, was tested in therapeutic models that were known to respond to D1 agonists. Because of a species difference in affinity for DETQ, all rodent experiments used transgenic mice expressing the human D1 receptor (hD1 mice). When given alone, DETQ reversed the locomotor depression caused by a low dose of reserpine. DETQ also acted synergistically with L-DOPA to reverse the strong hypokinesia seen with a higher dose of reserpine. These results indicate potential as both monotherapy and adjunct treatment in Parkinson's disease. DETQ markedly increased release of both acetylcholine and histamine in the prefrontal cortex, and increased levels of histamine metabolites in the striatum. In the hippocampus, the combination of DETQ and the cholinesterase inhibitor rivastigmine increased ACh to a greater degree than either agent alone. DETQ also increased phosphorylation of the AMPA receptor (GluR1) and the transcription factor CREB in the striatum, consistent with enhanced synaptic plasticity. In the Y-maze, DETQ increased arm entries but (unlike a D1 agonist) did not reduce spontaneous alternation between arms at high doses. DETQ enhanced wakefulness in EEG studies in hD1 mice and decreased immobility in the forced-swim test, a model for antidepressant-like activity. In rhesus monkeys, DETQ increased spontaneous eye-blink rate, a measure that is known to be depressed in Parkinson's disease. Together, these results provide support for potential utility of D1 potentiators in the treatment of several neuropsychiatric disorders, including Parkinson's disease, Alzheimer's disease, cognitive impairment in schizophrenia, and major depressive disorder.

An Allosteric Potentiator of the Dopamine D1 Receptor Increases Locomotor Activity in Human D1 Knock-In Mice without Causing Stereotypy or Tachyphylaxis.

Allosteric potentiators amplify the sensitivity of physiologic control circuits, a mode of action that could provide therapeutic advantages. This hypothesis was tested with the dopamine D1 receptor potentiator DETQ [2-(2,6-dichlorophenyl)-1-((1S,3R)-3-(hydroxymethyl)-5-(2-hydroxypropan-2-yl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one]. In human embryonic kidney 293 (HEK293) cells expressing the human D1 receptor, DETQ induced a 21-fold leftward shift in the cAMP response to dopamine, with a Kb of 26 nM. The maximum response to DETQ alone was ∼12% of the maximum response to dopamine, suggesting weak allosteric agonist activity. DETQ was ∼30-fold less potent at rat and mouse D1 receptors and was inactive at the human D5 receptor. To enable studies in rodents, an hD1 knock-in mouse was generated. DETQ (3-20 mg/kg orally) caused a robust (∼10-fold) increase in locomotor activity (LMA) in habituated hD1 mice but was inactive in wild-type mice. The LMA response to DETQ was blocked by the D1 antagonist SCH39166 and was dependent on endogenous dopamine. LMA reached a plateau at higher doses (30-240 mg/kg) even though free brain levels of DETQ continued to increase over the entire dose range. In contrast, the D1 agonists SKF 82958, A-77636, and dihydrexidine showed bell-shaped dose-response curves with a profound reduction in LMA at higher doses; video-tracking confirmed that the reduction in LMA caused by SKF 82958 was due to competing stereotyped behaviors. When dosed daily for 4 days, DETQ continued to elicit an increase in LMA, whereas the D1 agonist A-77636 showed complete tachyphylaxis by day 2. These results confirm that allosteric potentiators may have advantages compared with direct-acting agonists.

The cost of excessive postoperative use of antimicrobials: the context of a public hospital.

OBJECTIVE: To evaluate the improper use of antimicrobials during the postoperative period and its economic impact. METHODS: We conducted a prospective cohort study by collecting data from medical records of 237 patients operated on between 01/11/08 and 31/12/08. RESULTS: from the 237 patients with the information collected, 217 (91.56%) received antimicrobials. During the postoperative period, 125 (57.7%) patients received more than two antimicrobials. On average, 1.7 ± 0.6 antimicrobials were prescribed to patients, the most commonly prescribed antibiotic being cephalothin, in 41.5% (154) of cases. The direct cost of antimicrobial therapy accounted for 63.78% of all drug therapy, this large percentage being attributed in part to the extended antimicrobial prophylaxis. In the case of clean operations, where there was a mean duration of 5.2 days of antibiotics, antimicrobials represented 44.3% of the total therapy cost. CONCLUSION: The data illustrate the impact of overuse of antimicrobials, with questionable indications, creating situations that compromise patient safety and increasing costs in the assessed hospital.

The cost of excessive postoperative use of antimicrobials: the context of a public hospital / Consequências do uso excessivo de antimicrobianos no pós-operatório: o contexto de um hospital público

OBJECTIVE: To evaluate the improper use of antimicrobials during the postoperative period and its economic impact. METHODS: We conducted a prospective cohort study by collecting data from medical records of 237 patients operated on between 01/11/08 and 31/12/08. RESULTS: from the 237 patients with the information collected, 217 (91.56%) received antimicrobials. During the postoperative period, 125 (57.7%) patients received more than two antimicrobials. On average, 1.7 ± 0.6 antimicrobials were prescribed to patients, the most commonly prescribed antibiotic being cephalothin, in 41.5% (154) of cases. The direct cost of antimicrobial therapy accounted for 63.78% of all drug therapy, this large percentage being attributed in part to the extended antimicrobial prophylaxis. In the case of clean operations, where there was a mean duration of 5.2 days of antibiotics, antimicrobials represented 44.3% of the total therapy cost. CONCLUSION: The data illustrate the impact of overuse of antimicrobials, with questionable indications, creating situations that compromise patient safety and increasing costs in the assessed hospital. .

OBJETIVO: avaliar o emprego de antimicrobianos relacionado ao seu uso inadequado e impacto econômico durante o período pós-operatório. MÉTODOS: foi desenvolvido um estudo de coorte prospectivo por meio da coleta de dados de 237 prontuários de pacientes operados entre 01/11/08 e 31/12/08. RESULTADOS: dos 237 pacientes com informações coletadas no estudo 217 (91,56%) fizeram uso de antimicrobianos. Durante o pós-operatório, 125 (57,7%) pacientes utilizaram mais de dois antimicrobianos. Foi prescrito, em média, 1,7 ± 0,6 antimicrobianos por paciente, sendo o antimicrobiano mais prescrito a cefalotina, em 41,5% (154) dos casos. O custo direto da terapia antimicrobiana representou 63,78% de toda a terapia farmacológica, sendo esta grande porcentagem atribuída em parte ao prolongamento da profilaxia antimicrobiana. No caso das operações limpas, onde houve um tempo médio de uso de antimicrobianos de 5,2 dias, os gastos com antimicrobianos representaram 44,3% do custo total da terapia. . CONCLUSÃO: os dados exemplificam o impacto do uso excessivo de antimicrobianos, com indicações questionáveis e criando situações que comprometem a segurança dos pacientes e aumento os custos no hospital avaliado. .

LSN2424100: a novel, potent orexin-2 receptor antagonist with selectivity over orexin-1 receptors and activity in an animal model predictive of antidepressant-like efficacy.

We describe a novel, potent and selective orexin-2 (OX2)/hypocretin-2 receptor antagonist with in vivo activity in an animal model predictive of antidepressant-like efficacy. N-biphenyl-2-yl-4-fluoro-N-(1H-imidazol-2-ylmethyl) benzenesulfonamide HCl (LSN2424100) binds with high affinity to recombinant human OX2 receptors (Ki = 4.5 nM), and selectivity over OX1 receptors (Ki = 393 nM). LSN2424100 inhibited OXA-stimulated intracellular calcium release in HEK293 cells expressing human and rat OX2 receptors (Kb = 0.44 and 0.83 nM, respectively) preferentially over cells expressing human and rat OX1 (Kb = 90 and 175 nM, respectively). LSN2424100 exhibits good exposure in Sprague-Dawley rats after IP, but not PO, administration of a 30 mg/kg dose (AUC0-6 h = 1300 and 269 ng(*)h/mL, respectively). After IP administration in rats and mice, LSN2424100 produces dose-dependent antidepressant-like activity in the delayed-reinforcement of low-rate (DRL) assay, a model predictive of antidepressant-like efficacy. Efficacy in the DRL model was lost in mice lacking OX2, but not OX1 receptors, confirming OX2-specific activity. Importantly, antidepressant-like efficacy of the tricyclic antidepressant, imipramine, was maintained in both OX1 and OX2 receptor knock-out mice. In conclusion, the novel OX2 receptor antagonist, LSN2424100, is a valuable tool compound that can be used to explore the role of OX2 receptor-mediated signaling in mood disorders.

Controle de infecção no centro de tratamento de queimados: revisão de literatura / Infection control in burn center: review of the literature

Objetivo: Estudo que revisou as principais condutas de controle de infecção hospitar relacionadas à assistência de enfermagem no Centro de Tratamento de Queimados. Método: Revisão bibliográfica, com busca em bases de dados eletrônicas, num recorte temporal entre 2000 a 2011, e de publicações referentes às recomendações da Sociedade Brasileira de Queimaduras. Foram encontradas 67 publicações que, após a análise e aplicação dos critérios de inclusão, resultaram em 13. Resultados: Foram evidenciadas duas categorias: micro-organismos associados à infecção em queimaduras e controle de infecção no ambiente do Centro de Tratamento de Queimados. Conclusão: Ações de enfermagem visando à implementação de medidas de preventivas de infecção são essenciais para o cuidado ao paciente queimado.

Aim: This study aimed to review the control management of hospital infection related to nursing care in a Burn Center. Method: Literature review, with search in electronic databases, a time frame from 2000 to 2011, and related publications the recommendations of the Brazilian Society of Burns. We found 67 publications that after the analysis and application of the inclusion criteria resulted in 13. Results: The results showed two categories: micro-organisms associated with infection in burns and infection control in the environment of the Burn Center. Conclusions: Nursing actions forimplementation of preventive measures for infection is essential for the careof burn patients.