Noncontingent reinforcement in the treatment of pediatric feeding disorder: A concise review.

This concise review summarizes the literature on noncontingent reinforcement in the treatment of pediatric feeding disorder from 2018 to 2022. We reviewed 15 published behavior-analytic feeding studies to identify how often the term noncontingent reinforcement is used, what form of noncontingent reinforcement is delivered, and what the effects of noncontingent reinforcement are on behavior when it is included in treatment. Implications and directions for future research are discussed.

ENSEMBLE PLUS: final results of shorter ocrelizumab infusion from a randomized controlled trial.

INTRODUCTION: Ocrelizumab is an approved intravenously administered anti-CD20 antibody for multiple sclerosis (MS). The safety profile and patient preference for conventional versus shorter ocrelizumab infusions were investigated in the ENSEMBLE PLUS study. METHODS: ENSEMBLE PLUS was a randomized, double-blind substudy to the single-arm ENSEMBLE study (NCT03085810), comparing outcomes in patients with early-stage relapsing-remitting MS receiving ocrelizumab 600 mg over the approved 3.5-h (conventional) versus 2-h (shorter) infusion. The primary endpoint was the proportion of patients with infusion-related reactions (IRRs) following the first randomized dose (RD); the secondary endpoint included IRR frequency at subsequent RDs. RESULTS: At first RD, the number of patients with an IRR in the conventional (101/373; 27.1%) versus shorter (107/372; 28.8%) infusion group was similar (difference, stratified estimates [95% CI]: 1.9% [- 4.4, 8.2]). Most IRRs (conventional: 99.4%; shorter: 97.7%) were mild/moderate. IRR frequency decreased over the course of RDs; three patients discontinued from the shorter infusion arm but continued with conventional infusion. Overall, > 98% of IRRs resolved without sequelae in both groups. Pre-randomization throat irritation was predictive of future throat irritation as an IRR symptom. Adverse events (AEs) and serious AEs were consistent with the known ocrelizumab safety profile. On completion of ENSEMBLE PLUS, most patients chose to remain on (95%) or switch to (80%) shorter infusion. CONCLUSION: ENSEMBLE PLUS demonstrates the safety and tolerability of shorter ocrelizumab infusions. Most patients remained on/switched to shorter infusion after unblinding; IRRs did not strongly influence patient decisions. CLINICAL TRIALS REGISTRATION: Substudy of ENSEMBLE (NCT03085810). REGISTRATION: March 21, 2017.

A Continuum of Methods for Assessing Preference for Conversation Topics.

Among individuals with a diagnosis of autism spectrum disorders (ASD), conversation topic preference could influence social skills in many ways. For example, an individual with advanced vocal-verbal skills, but just learning to join a conversation, might be less inclined to participate if the topic chosen is not preferred. However, commonly used preference assessment procedures have not been applied to evaluating conversation-topic preferences. Therefore, the purpose of the current experiment was to conduct three different types of assessments that varied in efficiency, the degree of certainty they allow, and clients with whom they are likely to be applicable and acceptable. In particular, we conducted a self-report preference assessment, a multiple-stimulus-without-replacement (MSWO) preference assessment, and a response restriction conversation assessment (RRCA). Each assessment identified a preferred topic of conversation, but the RRCA was the only assessment that was able to differentiate which topics would maintain a conversation. Implications for assessment and intervention procedures related to complex social skills are discussed and directions for future research are proposed.

Reflections and Critical Directions for Toilet Training in Applied Behavior Analysis.

Achieving toileting independence is a critical skill that yields several benefits of pressing social, developmental, and health-related importance. The seminal behavioral approach to toilet training established the conceptualization of continence and framework for toileting research thereafter. Contemporary researchers continue to evaluate toilet training procedures that produce efficacious outcomes for young children that closely align with current applied behavior analysis (ABA) ethics and standards of practice. Despite the overall success of behavior-analytic toileting approaches, there are critical directions still worthy of consideration and investigation. In this paper, we acknowledge the seminal roots and many of the contemporary contributions. We also critically reflect on current practices while proposing necessary areas to advance behavior-analytic toilet training research.

Evaluation of schedule thinning following treatment for aggression maintained by access to higher level restrictive and repetitive behavior.

One of the diagnostic characteristics of individuals with autism spectrum disorders includes engaging in restricted and repetitive behavior. Research has shown that individuals will often display problem behavior when access to restricted and repetitive behavior is blocked. The purpose of the current study was to evaluate the use of functional communication training and schedule thinning to treat aggression displayed by three children diagnosed with autism spectrum disorders when higher level restrictive and repetitive behavior was blocked. Further, we assessed whether all steps in a schedule-thinning sequence were necessary as well as extended the practicality of these procedures by removing the continuous signal during the delay to reinforcement. The results indicated that functional communication with schedule thinning reduced aggression related to blocking access to engaging in higher level restrictive and repetitive behavior for all participants.

Recommendations Regarding Use of the Term "Ignore" in Applied Behavior Analysis.

Ignore is a common term used in behavioral assessment, behavior intervention plans, textbooks, and research articles. In the present article, we recommend against the typical usage of the term in most applications of behavior analysis. First, we briefly outline some history of the use of the term in behavior analysis. Then, we describe six main concerns about ignore and the implications for its continued use. Finally, we address each of these concerns with proposed solutions, such as alternatives to the use of ignore.

Verbal Behavior Analysis of Teaching Story Recall to Children with Autism: A Replication and Extension.

Children with autism spectrum disorder (ASD) may struggle with verbal behavior related to recall in various contexts. However, relatively little research has evaluated methods for improving recall among this population, and even fewer from a verbal behavior perspective. One socially important set of skills that relies upon a behavioral repertoire of recall is applied reading skills, such as reading comprehension and story recall. Valentino et al. (2015) designed an intervention package to teach children with ASD to recall short stories and conceptualized the behavior as an intraverbal chain. The present study replicated and extended that study with three school-aged children with ASD using a multiple baseline design across stories. For some participants and some stories, story recall was mastered under less intensive intervention conditions than in the previous study. When it was necessary to implement the full intervention package, the effects largely replicated previous research. Improvements in recall were correlated with increases in correct answers to comprehension questions. These data have important implications for clinicians and educators providing reading and recall interventions to children with ASD. Results also have theoretical implications for verbal behavior accounts of memory and recall, and suggest several possible avenues for future research. Supplementary Information: The online version contains supplementary material available at 10.1007/s40616-023-00183-2.

A Comparison of Baseline Procedures in Task Analyses.

Several methods for assessing baseline performance in chained tasks have been outlined in the literature, including the fixed-opportunity probe (FOP) and the multiple-opportunity probe (MOP). Concerns have been raised regarding how each of these methods might change the baseline performance of a task, affecting the interpretation of experimental control. The purpose of the current study was to conduct a within-subject comparison of both the FOP and MOP procedures for children with autism performing daily living and self-care skills. Results indicated that, for most participants, the MOP resulted in elevated performance during baseline compared to the FOP, and that for some participants the MOP resulted in acquisition prior to direct training. Because of the possibility that the FOP might result in suppressed baseline performance, it is recommended that in most cases clinicians and researchers use the MOP when assessing baseline performance in chained tasks in order to obtain the most accurate data.

Multiple sclerosis plasma IgG aggregates induce complement-dependent neuronal apoptosis.

Grey matter pathology is central to the progression of multiple sclerosis (MS). We discovered that MS plasma immunoglobulin G (IgG) antibodies, mainly IgG1, form large aggregates (>100 nm) which are retained in the flow-through after binding to Protein A. Utilizing an annexin V live-cell apoptosis detection assay, we demonstrated six times higher levels of neuronal apoptosis induced by MS plasma IgG aggregates (n = 190, from two cohorts) compared to other neurological disorders (n = 116) and healthy donors (n = 44). MS IgG aggregate-mediated, complement-dependent neuronal apoptosis was evaluated in multiple model systems including primary human neurons, primary human astrocytes, neuroblastoma SH-SY5Y cells, and newborn mouse brain slices. Immunocytochemistry revealed the co-deposition of IgG, early and late complement activation products (C1q, C3b, and membrane attack complex C5b9), as well as active caspase 3 in treated neuronal cells. Furthermore, we found that MS plasma cytotoxic antibodies are not present in Protein G flow-through, nor in the paired plasma. The neuronal apoptosis can be inhibited by IgG depletion, disruption of IgG aggregates, pan-caspase inhibitor, and is completely abolished by digestion with IgG-cleaving enzyme IdeS. Transmission electron microscopy and nanoparticle tracking analysis revealed the sizes of MS IgG aggregates are greater than 100 nm. Our data support the pathological role of MS IgG antibodies and corroborate their connection to complement activation and axonal damage, suggesting that apoptosis may be a mechanism of neurodegeneration in MS.

An evaluation of methods for studying the effects of conditioned reinforcement on human choice.

Shahan et al. (2006) found that the relative rate of pigeons' pecking on two observing responses (i.e., responses that only produced an S+ or stimulus correlated with primary reinforcement) was well described by the relative rate of S+ delivery. Researchers have not evaluated the effects of S+ delivery rate in a concurrent observing response procedure with human subjects, so the necessary procedural modifications for studying the effects of conditioned reinforcement on human choice remain unclear. The purpose of the current study was to conduct an additive component analysis of modifications to the procedures of Shahan et al. (2006). We evaluated the additive effects of introducing response cost, a changeover response, and ordinal discriminative stimuli on correspondence with the results of Shahan et al. and the quality of fits of the generalized matching equation. When our procedures were most similar to those of Shahan et al., we observed low rates of observing and indifference between the two observing responses. For the group of subjects with whom all three additive components were included, we obtained the highest level of sensitivity to relative rate of S+ delivery, but the slope and R2 of our fits of the generalized matching equation were still much lower than those obtained by Shahan et al. Potential reasons for these discrepancies, methods of resolving them, and implications for future research are discussed.

Safety and patient experience with at-home infusion of ocrelizumab for multiple sclerosis.

OBJECTIVE: This study aimed to evaluate safety (infusion-related reactions [IRRs]) and patient satisfaction (patient-reported outcomes [PROs]) for at-home ocrelizumab administration for patients with multiple sclerosis (MS). METHODS: This open-label study included adult patients with an MS diagnosis who had completed a ≥ 600-mg ocrelizumab dose, had a patient-determined disease steps score of 0 to 6 and had completed PROs. Eligible patients received a 600-mg ocrelizumab home-based infusion over 2 h, followed by 24-h and 2-week post-infusion follow-up calls. IRRs and adverse events (AEs) were documented during infusions and follow-up calls. PROs were completed before and 2 weeks post infusion. RESULTS: Overall, 99 of 100 expected patients were included (mean [SD] age, 42.3 [7.7] years; 72.7% female; 91.9% White). The mean (SD) infusion time was 2.5 (0.6) hours, and 75.8% of patients completed their ocrelizumab infusion between 2 to 2.5 h. The IRR incidence rate was 25.3% (95% CI: 16.7%, 33.8%)-similar to other shorter ocrelizumab infusion studies-and all AEs were mild/moderate. In total, 66.7% of patients experienced AEs, including itch, fatigue, and grogginess. Patients reported significantly increased satisfaction with the at-home infusion process and confidence in the care provided. Patients also reported a significant preference for at-home infusion compared with prior infusion center experiences. INTERPRETATION: IRRs and AEs occurred at acceptable rates during in-home infusions of ocrelizumab over a shorter infusion time. Patients reported increased confidence and comfort with the home infusion process. Findings from this study provide evidence of the safety and feasibility of home-based ocrelizumab infusion over a shorter infusion period.

An Assessment of Response to Conversation Cues of Uninterest Conducted via Telehealth.

Individuals diagnosed with autism spectrum disorder (ASD) exhibit deficits in social interaction and communication. Kronfli, Vollmer, et al. developed an in-person assessment to evaluate participant response to social cues indicating uninterest in a conversation. In the current study, we sought to extend these procedures to the assessment of conversation skills via telehealth given the ongoing pandemic and so that participants in remote areas could receive services. Participants were exposed to a hierarchy of social cues of uninterest ranging in salience from one-word responses to a clear verbal statement of uninterest until they demonstrated sensitivity to a social cue. One participant who did not demonstrate sensitivity to any cues received instruction using Behavioral Skills Training. Initial results support the utility of using a remote assessment model to screen for sensitivity to specific social cues in conversations and to provide services to participants via telehealth.

A Brief Assessment to Identify Sensitivity to a Conversational Partner's Interest.

Individuals diagnosed with autism spectrum disorder (ASD) may seek professional assistance with social skills, such as identifying the function of social cues and responding appropriately to those cues. The purpose of the current study was to develop a brief assessment to determine participant sensitivity to social cues indicating uninterest in continuing a conversation. Results show that the assessment was successful in identifying contexts to address on an individual basis, related to social cues during conversation. Furthermore, the assessment fit within an hourly appointment appropriate for individuals with ASD (we used person-first or identify-first language based on caregiver and individual preference) who display sophisticated conversational repertoires. Future research should evaluate the content of the conversations and other nonvocal stimuli that might be beneficial in assisting with social interactions, in addition to using behavioral skills training to strengthen the specific social skills evaluated in the current study.

High-Efficacy Therapies for Treatment-Naïve Individuals with Relapsing-Remitting Multiple Sclerosis.

There are > 18 distinct disease-modifying therapy (DMT) options covering 10 mechanisms of action currently approved by the US Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis (RRMS). Given the multitude of available treatment options, and recent international consensus guidelines offering differing recommendations, there is broad heterogeneity in how the DMTs are used in clinical practice. Choosing a DMT for newly diagnosed patients with MS is currently a topic of significant debate in MS care. Historically, an escalation approach to DMT was used for newly diagnosed patients with RRMS. However, the evidence for clinical benefits of early treatment with high-efficacy therapies (HETs) in this population is emerging. In this review, we provide an overview of the DMT options and MS treatment strategies, and discuss the clinical benefits of HETs (including ofatumumab, ocrelizumab, natalizumab, alemtuzumab, and cladribine) in the early stages of MS, along with safety concerns associated with these DMTs. By minimizing the accumulation of neurological damage early in the disease course, early treatment with HETs may enhance long-term clinical outcomes over the lifetime of the patient.

Disease-modifying therapies (DMTs) can help people with multiple sclerosis (MS) by changing the way that their MS develops over time. Some people with MS have relapses when their symptoms get worse, followed by recovery when their MS is remitting. This is called relapsing­remitting MS (RRMS). DMTs can reduce both the number and the severity of relapses. They can also delay the nerve damage that relapses cause. A range of DMTs are approved for treating people with RRMS. These treatments work in different ways, and international treatment guidelines vary on their recommendations for using DMTs in the clinic. Selecting DMTs for people with newly diagnosed RRMS is still a topic of discussion. Previously, people with RRMS only received the more effective high-efficacy therapies (HETs) if their first treatment was not effective. HETs include ofatumumab, ocrelizumab, natalizumab, alemtuzumab, and cladribine. Recently, using HETs at an earlier stage has shown promising results. In this review article, we provide an overview of the clinical strategies and the DMT options that are available for people with MS. Additionally, we discuss the benefits of using HETs for people with newly diagnosed MS and consider the safety issues related to DMTs. We summarize that using HETs to reduce the buildup of nerve damage during the early stages of MS may lead to improved long-term clinical outcomes over a person's lifetime.

Commentary on Slocum et al. (2022): Additional Considerations for Evaluating Experimental Control.

In the target article, Slocum et al. (2022) suggested that nonconcurrent multiple baseline designs can provide internal validity comparable to concurrent multiple baseline designs. We provide further support for this assertion; however, we highlight additional considerations for determining the relative strength of each design. We advocate for a more nuanced approach to evaluating design strength and less reliance on strict adherence to a specific set of rules because the details of the design only matter insofar as they help researchers convince others that the results are valid and accurate. We provide further support for Slocum et al.'s argument by emphasizing the relatively low probability that within-tier comparisons would fail to identify confounds. We also extend this logic to suggest that staggering implementation of the independent variable across tiers may be an unnecessary design feature in certain cases. In addition, we provide an argument that nonconcurrent multiple baseline designs may provide verification within baseline logic contrary to arguments made by previous researchers. Despite our general support for Slocum et al.'s assertions and our advocacy for more nuanced approaches to determining the strength of experimental designs, we urge experimenters to consider the perspectives of researchers from other fields who may favor concurrent multiple-baseline designs and suggest that using concurrent multiple-baseline designs when feasible may foster dissemination of behavior analytic research.

Pediatric Pain and Neurodevelopmental Disorders: Implications for Research and Practice in Behavior Analysis.

Individuals diagnosed with a neurodevelopmental disorder also are commonly diagnosed with a medical comorbidity. Because of this, it is estimated that this population experiences nearly twice the incidence of pain or discomfort as their neurotypical peers. Although behavior analysts consider the effect of biological variables on a client's behavior, considerations of pain appear to be underdiscussed and understudied. The purpose of this article is to discuss how pain may interact with the efficacy of behavior analytic assessments and treatments, provide potential solutions to the barriers associated with pain states, and describe avenues to promote clinical research to improve our behavior analysis of pediatric pain while developing treatments for behavior problems such as aggression.

The matching law provides a quantitative description of social time allocation in children with autism.

Recent research has developed and evaluated assessments of sociability in which time allocation near or away from an adult who initiates social interactions is used to characterize the participant as social, indifferent, or avoidant of social interaction. Though these qualitative outcomes have been useful, no studies have evaluated methods of obtaining more quantitative measures of sociability. The matching law has been demonstrated to describe a wide range of human behavior and may also be useful in describing social time allocation. We adapted the matching law and assessment of sociability procedures with the aim of providing a more precise, quantitative measure of sociability. We fitted the matching equation to the social time allocation data of 8 children with autism spectrum disorder. The equation was effective in quantifying sociability, accounted for a large proportion of variance in participants' behavior, did so equally well for participants who were social and avoidant, and provided a more sensitive measure relative to those used in previous research. The implications of this methodology, its potential utility, and directions for future research are discussed.

Further evaluation of functional analysis screening methods in early autism intervention.

A goal of some functional analysis (FA) variations is to reduce assessment time while still maintaining efficacy. This may be especially important when conducting FAs in early intervention programs, where time is a crucial commodity. To that end, we evaluated a model for using the results of the no-interaction condition as a screening for behavioral function and to guide selection of FA test conditions with 20 participants (22 assessments) aged 3 to 7 years old. We used the no-interaction condition to develop hypotheses for both automatic reinforcement and socially mediated reinforcement. The outcome of the no-interaction condition guided the selection of test conditions for the remainder of the FA. We also incorporated methods from prior FA studies (e.g., divided attention) to modify the test conditions. We obtained differentiated results in 91% of assessments, all within 70 min and, as such, extended evidence that an FA can be completed in little time without sacrificing efficacy.

New (old) perspectives on self-injurious and aggressive biting.

Functional analyses and treatments of self-injurious behavior and aggression have shown that such behavior is often operant. In this paper, we will revisit evidence that a subset of self-injurious and aggressive biting may be controlled primarily by antecedent events and may have phylogenetic origins. We propose that there is a research gap of more than four decades, if one considers the wealth of basic research on biting that occurred prior to 1977. To our knowledge, that body of basic research was never fully translated or directly applied within behavior analysis. It is known that organisms (including humans) sometimes bite in the presence of aversive events (broadly defined as the presentation of aversive stimuli or the removal of reinforcers). Thus, the variables controlling biting in the context of behavioral assessment and treatment require further analysis.