Deeply Tailoring Adaptive Interventions: Enhancing Knowledge Generation of SMARTs in Special Education

Special educators serve a diverse population of students with unique strengths and needs, and adaptive interventions that account for individual differences before and during the intervention are an important tool to moving the field toward more individualized practices. The purpose of this article is to detail the conceptualization and application of tailoring the sequential multiple assignment randomized trial (SMART) design approach to developing and evaluating deeply tailored adaptive interventions through the application of secondary analyses to account for individual differences at multiple time points. This conceptual paper provides an overview beyond the basic SMART design components by describing the tactics, design options, and analyses currently available to further refine a SMART study into a more personalized intervention to account for individual differences at multiple points throughout the intervention and individual response to treatment.

A Sequential Multiple Assignment Randomized Trial (SMART) study of medication and CBT sequencing in the treatment of pediatric anxiety disorders

Background Treatment of a child who has an anxiety disorder usually begins with the question of which treatment to start first, medication or psychotherapy. Both have strong empirical support, but few studies have compared their effectiveness head-to-head, and none has investigated what to do if the treatment tried first isn’t working well—whether to optimize the treatment already begun or to add the other treatment. Methods This is a single-blind Sequential Multiple Assignment Randomized Trial (SMART) of 24 weeks duration with two levels of randomization, one in each of two 12-week stages. In Stage 1, children will be randomized to fluoxetine or Coping Cat Cognitive Behavioral Therapy (CBT). In Stage 2, remitters will continue maintenance-level therapy with the single-modality treatment received in Stage 1. Non-remitters during the first 12 weeks of treatment will be randomized to either [1] optimization of their Stage 1 treatment, or [2] optimization of Stage 1 treatment and addition of the other intervention. After the 24-week trial, we will follow participants during open, naturalistic treatment to assess the durability of study treatment effects. Patients, 8–17 years of age who are diagnosed with an anxiety disorder, will be recruited and treated within 9 large clinical sites throughout greater Los Angeles. They will be predominantly underserved, ethnic minorities. The primary outcome measure will be the self-report score on the 41-item youth SCARED (Screen for Child Anxiety Related Disorders). An intent-to-treat analysis will compare youth randomized to fluoxetine first versus those randomized to CBT first (“Main Effect 1”). Then, among Stage 1 non-remitters, we will compare non-remitters randomized to optimization of their Stage 1 monotherapy versus non-remitters randomized to combination treatment (“Main Effect 2”). The interaction of these main effects will assess whether one of the 4 treatment sequences (CBT➔CBT; CBT➔med; med➔med; med➔CBT) in non-remitters is significantly better or worse than predicted from main effects alone. Discussion Findings from this SMART study will identify treatment sequences that optimize outcomes in ethnically diverse pediatric patients from underserved low- and middle-income households who have anxiety disorders. Trial registration This protocol, version 1.0, was registered in ClinicalTrials.gov on February 17, 2021 with Identifier: NCT04760275.

Prosocial Choices: How Do Young Children Evaluate (In)Considerate Behavior?

Adults often act considerately towards others by, for example, leaving the last cookie on a plate or by stepping aside on a busy sidewalk. What do young children infer from such considerate behavior? In two preregistered studies, we assess how young children evaluate (in)considerate behavior by showing them animated videos in which targets make decisions that either leave or limit choice options for others. Specifically, in the videos one target decides to pick a unique object (e.g., picking the only toy boat) and therefore leaves no choice for someone else to pick that object. In contrast, the other target leaves a choice for someone else by picking a non-unique object (e.g., picking a toy train of which there are three). Study 1 (N = 372 6-to-12 year old children) showed that with age children evaluate considerate others (i.e., who leave a choice for others) as nicer and more trustworthy than inconsiderate others (i.e., who do not leave a choice for others). Moreover, children’s evaluations were specific to the social domain, as children of all ages evaluated both targets as equally smart. Study 2 (N = 99) focused on younger children (5-to-7-year-olds) and showed that when videos were presented in a simpler manner they also evaluated considerate people as nicer. These studies extend developmental research on prosocial behavior and suggest that considerate behavior conveys a clear social signal early in life.

Antimicrobial activity of ceftolozane-tazobactam against Enterobacterales and Pseudomonas aeruginosa recovered during the Study for Monitoring Antimicrobial Resistance Trends (SMART) program in Spain (2016-2018)

Objective. To analyse the susceptibility to ceftolozane-tazobactam and comparators in Enterobacterales and Pseudomonas aeruginosa isolates recovered from intraabdominal (IAI), urinary (UTI), respiratory (RTI) and bloodstream infection (BSI) in the SMART (Study for Monitoring Antimicrobial Resistance Trends) study. Methods. The susceptibility of 5,351 isolates collected in 11 Spanish hospitals (2016-2018) were analysed (EUCAST-2020 criteria) by broth microdilution and were phenotypically studied for the presence of extended-spectrum beta-lactamases (ESBL). Ceftolozane-tazobactam and/or carbapenem resistant isolates were genetically characterized for ESBL and carbapenemases. Results. Escherichia coli was the most frequent pathogen (49.3% IAI, 54.9% UTI, 16.7% RTI and 50% BSI), followed by Klebsiella pneumoniae (11.9%, 19.1%, 13.1% and 15.4%, respectively). P. aeruginosa was isolated in 9.3%, 5.6%, 32% and 9%, respectively. The frequency of isolates with ESBLs (2016-2017) was: 30.5% K. pneumoniae, 8.6% E. coli, 2.3% Klebsiella oxytoca and 0.7% Proteus mirabilis. Ceftolozane-tazobactam was very active against non-ESBL-(99.3% susceptible) and ESBL-(95.2%) producing E. coli being less active against K. pneumoniae (98% and 43.1%, respectively) isolates. CTX-M-15 was the most prevalent ESBL in E. coli (27.5%) and K. pneumoniae (51.9%) frequently associated with OXA-48-like carbapenemase. Overall, 93% of P. aeruginosa isolates were susceptible to ceftolozane-tazobactam, preserving this activity (>75%) in isolates resistant to other beta-lactams except in those resistant to meropenen or ceftazidime-avibactam. GES-5, PER-1, VIM-1/2 were the most prevalent enzymes in isolates resistant to ceftolozane-tazobactam. Conclusions. Ceftolozane-tazobactam showed high activity rates against isolates recovered in the SMART study although it was affected in K. pneumoniae and P. aeruginosa isolates with ESBL and/or carbapenemases.