Parent-led, stepped-care cognitive-behavioral therapy for youth with autism and co-occurring anxiety: study rationale and method

Anxiety disorders affect up to 50% of individuals with autism spectrum disorder (ASD) and are significantly impairing to the person affected, as well as to their loved ones. Cognitive-behavioral therapy (CBT) has been established as the gold-standard treatment for anxiety disorders among typically developing youth and adults, and demonstrates similar efficacy among youth with high-functioning autism (HFA). Many CBT interventions utilize a "full-package" treatment approach to treat co-occurring anxiety in youth with ASD. However, these service delivery systems are often therapist-intensive, costly, and impractical, thereby compromising full engagement and treatment adherence. This paper describes the design, rationale, and methodology of a study examining stepped-care CBT for youth with HFA and co-occurring anxiety - a clinical trial examining the efficacy of low-intensity, parent-led CBT as the first line of treatment and utilizing a more intensive, therapist-led intervention for nonresponders. The study will evaluate the potential benefits of stepped-care and parent-led therapist-assisted interventions, predictors of treatment response, and the economic value of using a stepped-care model. Implications for practice will be discussed.

Factors underlying the changing of antibiotics in a paediatric intensive care unit in Pietermaritzburg, KwaZulu-Natal

Background. Antibiotics are among the most commonly used drugs in a paediatric intensive care unit (PICU). Despite guidelines and protocols for the use of antibiotics, inappropriate use may contribute to an increase in antibiotic resistance. The factors behind changes in antibiotic prescriptions in the PICU at Grey's Hospital are unknown. Objective. To establish the frequency, process and rationale behind antibiotic prescription changes in the picu. Methods. A retrospective descriptive study of all eligible patients admitted to the PICU during a 6-month period.Results. Three-quarters of patients admitted to the PICU received antibiotics during their stay. The ofantibiotic prescription was changed in 80 (58%) of the138 patients, with most changes (63.4%) occurring within 3 days of admission. Patients younger than 1 year and those who were malnourished accounted for 57% of the changes. The majority (65%) of the changes entailed the escalation of antibiotics and 89% of these were empiric therapy. De-escalation accounted for 35% of the changes. The rationale for a prescription change was not documented in 80% of cases.Conclusion. Antibiotic use in this PICU and changes to prescriptions were common. Changes were generally made on an empirical basis soon after admission and were more likely to occur in young malnourished children and patients admitted for a medical reason or surgical emergency

Models for the recent evolution of protocadherin gene clusters

The clustered protocadherins (Pcdhs) are single-pass transmembrane proteins that constitute a subfamily within the cadherin superfamily. In mammals, they are arranged in three consecutive clusters named alpha, beta, and gamma. These proteins are expressed in the nervous system and are targeted to mature synapses.Interestingly, different neurons express different subsets of isoforms; however, little is known about the functions and expression of the clustered Pcdhs. Previous phylogenetic analyses that compared rodent and human clusters postulated the recent occurrence of gene duplication events. Using standard phylogenetic methods, I confirmed the prior observations, and I show that duplications are likely to occur through unequal crossing-over events between two, and sometimes three, different Pcdh genes. The results are consistent with the fact that these genes undergo gene conversion. Recombination events between different clustered Pcdh genes appear to underlie concerted evolution through gene conversion and gene duplications through unequal crossing-over. In this work, I provided evidence that the unit of duplication of these genes in both the mouse and the human and within each cluster is the same. The unit of duplication includes the extracellular domain-coding sequence of an isoform and its promoter along with the cytoplasmic domain-coding region of the immediately upstream isoform in the cluster.