A comparative effectiveness trial of functional behavioral assessment methods.

Clinicians report primarily using functional behavioral assessment (FBA) methods that do not include functional analyses. However, studies examining the correspondence between functional analyses and other types of FBAs have produced inconsistent results. In addition, although functional analyses are considered the gold standard, their contribution toward successful treatment compared with other FBA methods remains unclear. This comparative effectiveness study, conducted with 57 young children with autism spectrum disorder, evaluated the results of FBAs that did (n = 26) and did not (n = 31) include a functional analysis. Results of FBAs with and without functional analyses showed modest correspondence. All participants who completed functional communication training achieved successful outcomes regardless of the type of FBA conducted.

Development of a proteomic signature associated with severe disease for patients with COVID-19 using data from 5 multicenter, randomized, controlled, and prospective studies.

Significant progress has been made in preventing severe COVID-19 disease through the development of vaccines. However, we still lack a validated baseline predictive biologic signature for the development of more severe disease in both outpatients and inpatients infected with SARS-CoV-2. The objective of this study was to develop and externally validate, via 5 international outpatient and inpatient trials and/or prospective cohort studies, a novel baseline proteomic signature, which predicts the development of moderate or severe (vs mild) disease in patients with COVID-19 from a proteomic analysis of 7000 + proteins. The secondary objective was exploratory, to identify (1) individual baseline protein levels and/or (2) protein level changes within the first 2 weeks of acute infection that are associated with the development of moderate/severe (vs mild) disease. For model development, samples collected from 2 randomized controlled trials were used. Plasma was isolated and the SomaLogic SomaScan platform was used to characterize protein levels for 7301 proteins of interest for all studies. We dichotomized 113 patients as having mild or moderate/severe COVID-19 disease. An elastic net approach was used to develop a predictive proteomic signature. For validation, we applied our signature to data from three independent prospective biomarker studies. We found 4110 proteins measured at baseline that significantly differed between patients with mild COVID-19 and those with moderate/severe COVID-19 after adjusting for multiple hypothesis testing. Baseline protein expression was associated with predicted disease severity with an error rate of 4.7% (AUC = 0.964). We also found that five proteins (Afamin, I-309, NKG2A, PRS57, LIPK) and patient age serve as a signature that separates patients with mild COVID-19 and patients with moderate/severe COVID-19 with an error rate of 1.77% (AUC = 0.9804). This panel was validated using data from 3 external studies with AUCs of 0.764 (Harvard University), 0.696 (University of Colorado), and 0.893 (Karolinska Institutet). In this study we developed and externally validated a baseline COVID-19 proteomic signature associated with disease severity for potential use in both outpatients and inpatients with COVID-19.

Patient Outcomes and Unit Composition With Transition to a High-Intensity ICU Staffing Model: A Before-and-After Study.

Provider staffing models for ICUs are generally based on pragmatic necessities and historical norms at individual institutions. A better understanding of the role that provider staffing models play in determining patient outcomes and optimizing use of ICU resources is needed. OBJECTIVES: To explore the impact of transitioning from a low- to high-intensity intensivist staffing model on patient outcomes and unit composition. DESIGN SETTING AND PARTICIPANTS: This was a prospective observational before-and-after study of adult ICU patients admitted to a single community hospital ICU before (October 2016-May 2017) and after (June 2017-November 2017) the transition to a high-intensity ICU staffing model. MAIN OUTCOMES AND MEASURES: The primary outcome was 30-day all-cause mortality. Secondary outcomes included in-hospital mortality, ICU length of stay (LOS), and unit composition characteristics including type (e.g., medical, surgical) and purpose (ICU-specific intervention vs close monitoring only) of admission. RESULTS: For the primary outcome, 1,219 subjects were included (779 low-intensity, 440 high-intensity). In multivariable analysis, the transition to a high-intensity staffing model was not associated with a decrease in 30-day (odds ratio [OR], 0.90; 95% CI, 0.61-1.34; p = 0.62) or in-hospital (OR, 0.89; 95% CI, 0.57-1.38; p = 0.60) mortality, nor ICU LOS. However, the proportion of patients admitted to the ICU without an ICU-specific need did decrease under the high-intensity staffing model (27.2% low-intensity to 17.5% high-intensity; p < 0.001). CONCLUSIONS AND RELEVANCE: Multivariable analysis showed no association between transition to a high-intensity ICU staffing model and mortality or LOS outcomes; however, the proportion of patients admitted without an ICU-specific need decreased under the high-intensity model. Further research is needed to determine whether a high-intensity staffing model may lead to more efficient ICU bed usage.

Efficacy of Losartan in Hospitalized Patients With COVID-19-Induced Lung Injury: A Randomized Clinical Trial.

Importance: SARS-CoV-2 viral entry may disrupt angiotensin II (AII) homeostasis, contributing to COVID-19 induced lung injury. AII type 1 receptor blockade mitigates lung injury in preclinical models, although data in humans with COVID-19 remain mixed. Objective: To test the efficacy of losartan to reduce lung injury in hospitalized patients with COVID-19. Design, Setting, and Participants: This blinded, placebo-controlled randomized clinical trial was conducted in 13 hospitals in the United States from April 2020 to February 2021. Hospitalized patients with COVID-19 and a respiratory sequential organ failure assessment score of at least 1 and not already using a renin-angiotensin-aldosterone system (RAAS) inhibitor were eligible for participation. Data were analyzed from April 19 to August 24, 2021. Interventions: Losartan 50 mg orally twice daily vs equivalent placebo for 10 days or until hospital discharge. Main Outcomes and Measures: The primary outcome was the imputed arterial partial pressure of oxygen to fraction of inspired oxygen (Pao2:Fio2) ratio at 7 days. Secondary outcomes included ordinal COVID-19 severity; days without supplemental o2, ventilation, or vasopressors; and mortality. Losartan pharmacokinetics and RAAS components (AII, angiotensin-[1-7] and angiotensin-converting enzymes 1 and 2)] were measured in a subgroup of participants. Results: A total of 205 participants (mean [SD] age, 55.2 [15.7] years; 123 [60.0%] men) were randomized, with 101 participants assigned to losartan and 104 participants assigned to placebo. Compared with placebo, losartan did not significantly affect Pao2:Fio2 ratio at 7 days (difference, -24.8 [95%, -55.6 to 6.1]; P = .12). Compared with placebo, losartan did not improve any secondary clinical outcomes and led to fewer vasopressor-free days than placebo (median [IQR], 9.4 [9.1-9.8] vasopressor-free days vs 8.7 [8.2-9.3] vasopressor-free days). Conclusions and Relevance: This randomized clinical trial found that initiation of orally administered losartan to hospitalized patients with COVID-19 and acute lung injury did not improve Pao2:Fio2 ratio at 7 days. These data may have implications for ongoing clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT04312009.

Cinematic virtual reality for anxiety management in mechanically ventilated patients: a feasibility and pilot study.

BACKGROUND: Mechanically ventilated patients experience anxiety for many reasons. Pharmacological treatments such as benzodiazepines are commonly employed to manage anxiety; however, these therapies often cause undesired side effects. Additional therapies for anxiety management are needed. We sought to determine whether cell phone-based virtual reality therapy could feasibly be used for anxiety management in mechanically ventilated patients. METHODS: Mechanically ventilated subjects underwent at least one session of virtual reality therapy in which they were shown a cinematic video of an outdoor green space or blue space with 360° visual range of motion. Goal session duration was 5 minutes. The primary outcome was incidence of predefined patient safety events, including self-extubation and accidental removal of tubes or lines. RESULTS: Ten subjects underwent a total of 18 virtual reality sessions. Fifteen sessions lasted the planned 5 minutes, one session was extended at participant request, and two sessions were terminated early at participant request. There were no occurrences of the predefined safety events, and no occurrences of cybersickness. Use of a visual analog scale to measure anxiety level was feasible for this pilot study, demonstrating feasibility of this scale for future, larger scale studies. CONCLUSIONS: Virtual reality therapy shows potential as a means of managing anxiety in patients undergoing mechanical ventilation, and further rigorous exploration with this protocol is feasible.

Evaluating Vitamin C in Septic Shock: A Randomized Controlled Trial of Vitamin C Monotherapy.

OBJECTIVES: To determine whether IV vitamin C therapy reduces 28-day mortality in patients with septic shock. DESIGN: Multicenter, double-blinded, randomized controlled trial. SETTING: One academic medical ICU and four community ICUs. PATIENTS: Of 167 adult patients within 24 hours of vasopressor initiation for septic shock, 126 consented to participation, and 124 received study drug and were included in analysis. INTERVENTIONS: IV vitamin C (10 mg/mL in normal saline) administered as a 1,000-mg bolus over 30 minutes followed by continuous infusion of 250 mg/hr for 96 hours or placebo of equal volumes of normal saline. MEASUREMENTS AND MAIN RESULTS: Of 124 subjects receiving study drug and included in analysis, 60 received vitamin C and 64 placebo. The primary outcome of all-cause 28-day mortality (vitamin C, 26.7%; placebo, 40.6%; p = 0.10) was lower in the vitamin C arm but did not reach statistical significance. Initiation of renal replacement therapy was higher in the vitamin C arm (vitamin C, 16.7%; placebo, 3.3%; p = 0.015), as was volume of fluid administration within 6 hours of study drug initiation (vitamin C, 1.07 L; placebo, 0.76 L; p = 0.03). There were no statistically significant differences in other secondary outcomes. In post hoc subgroup analysis, there was a decrease in 28-day mortality in the vitamin C arm among patients requiring positive-pressure ventilation at the time of enrollment (vitamin C, 36.3%; placebo, 60.0%; p = 0.05). This trial is registered at clinicaltrials.gov under identifier NCT03338569. CONCLUSIONS: Vitamin C monotherapy failed to significantly reduce mortality in septic shock patients as hypothesized. Our findings do not support its routine clinical use for this purpose.

Parent Ratings of Generalized and Indirect Effects of Functional Communication Training for Children with Autism Spectrum Disorder.

Functional communication training (FCT) is a behavioral treatment that has been shown to reduce problem behavior and increase appropriate communication in young children with autism spectrum disorder (ASD). In this study, we assessed the effects of FCT on targeted and nontargeted problem behaviors outside of the training context, as well as parent stress, for 30 young children with ASD and their parents. Indirect measures of generalization treatment effects were administered prior to and following FCT treatment delivered via telehealth. Children demonstrated significant improvement on both targeted (measured via observation) and nontargeted (measured via checklist) problem behaviors, both within and outside of the training context, and parent stress was significantly reduced following treatment. These results suggest that the impact of FCT may extend beyond the training context for both the children being treated and the parents delivering treatment, even when generalization is not specifically programmed for during treatment.

A multi-center phase II randomized clinical trial of losartan on symptomatic outpatients with COVID-19.

BACKGROUND: The SARS-CoV-2 virus enters cells via Angiotensin-converting enzyme 2 (ACE2), disrupting the renin-angiotensin-aldosterone axis, potentially contributing to lung injury. Treatment with angiotensin receptor blockers (ARBs), such as losartan, may mitigate these effects, though induction of ACE2 could increase viral entry, replication, and worsen disease. METHODS: This study represents a placebo-controlled blinded randomized clinical trial (RCT) to test the efficacy of losartan on outpatients with COVID-19 across three hospital systems with numerous community sites in Minnesota, U.S. Participants included symptomatic outpatients with COVID-19 not already taking ACE-inhibitors or ARBs, enrolled within 7 days of symptom onset. Patients were randomized to 1:1 losartan (25 mg orally twice daily unless estimated glomerular filtration rate, eGFR, was reduced, when dosing was reduced to once daily) versus placebo for 10 days, and all patients and outcome assesors were blinded. The primary outcome was all-cause hospitalization within 15 days. Secondary outcomes included functional status, dyspnea, temperature, and viral load. (clinicatrials.gov, NCT04311177, closed to new participants). FINDINGS: From April to November 2020, 117 participants were randomized 58 to losartan and 59 to placebo, and all were analyzed under intent to treat principles. The primary outcome did not differ significantly between the two arms based on Barnard's test [losartan arm: 3 events (5.2% 95% CI 1.1, 14.4%) versus placebo arm: 1 event (1.7%; 95% CI 0.0, 9.1%)]; proportion difference -3.5% (95% CI -13.2, 4.8%); p = 0.32]. Viral loads were not statistically different between treatment groups at any time point. Adverse events per 10 patient days did not differ signifcantly [0.33 (95% CI 0.22-0.49) for losartan vs. 0.37 (95% CI 0.25-0.55) for placebo]. Due to a lower than expected hospitalization rate and low likelihood of a clinically important treatment effect, the trial was terminated early. INTERPRETATION: In this multicenter blinded RCT for outpatients with mild symptomatic COVID-19 disease, losartan did not reduce hospitalizations, though assessment was limited by low event rate. Importantly, viral load was not statistically affected by treatment. This study does not support initiation of losartan for low-risk outpatients.

Delivering Interventions Via Telehealth: Functional Communication Training with a Child with Autism as a Case Example.

In this article, we provide a case example of how telehealth can be used by care providers in their homes to access empirically validated procedures such as functional communication training. As shown in the case example, complex assessment and intervention procedures were implemented successfully by care providers in their homes while receiving real-time coaching by behavior analysts who were located in a hospital in a different city. This case example is representative of the results we obtained thus far; substantial improvements in challenging and adaptive behavior occurred. Given these results obtained to date with telehealth, in terms of both outcomes of interventions and rated acceptability of the procedures by care providers, further and more widespread application of telehealth is warranted.

Functional assessment and function-based treatment delivered via telehealth: A brief summary.

As the world navigates the COVID-19 health crisis, behavior analysts are considering how best to support families while maintaining services and ensuring the health and safety of everyone involved. Telehealth is one service delivery option that provides families with access to care in their own communities and homes. In this article, we provide a brief summary of the telehealth literature in applied behavior analysis that provided coaching and training to families for individuals who displayed challenging behavior. These studies targeted functional assessment and function-based treatment for challenging behavior. We briefly summarize what is known relative to the assessment and treatment of challenging behavior via telehealth, place these results within a descriptive context of the decisions made by the research team at the University of Iowa, and discuss what we, as behavior analysts, should consider next to advance our understanding and practice of telehealth.

A Randomized Controlled Trial of Functional Communication Training via Telehealth for Young Children with Autism Spectrum Disorder.

Many children with autism spectrum disorder (ASD) have problem behaviors that interfere with learning and social interaction. This randomized controlled trial compared treatment with functional communication training (FCT) to "treatment as usual" for young children with ASD (n = 38, ages 21-84 months). FCT was conducted by parents with training and real-time coaching provided by behavioral consultants using telehealth. FCT treatment via telehealth achieved a mean reduction in problem behavior of 98% compared to limited behavioral improvement in children receiving "treatment as usual" during a 12-week period. Social communication and task completion also improved. For children with ASD and moderate to severe behavior problems, parent-implemented FCT using telehealth significantly reduced problem behavior while ongoing interventions typically did not.

An evaluation of resurgence following functional communication training conducted in alternative antecedent contexts via telehealth.

Treatments based on differential reinforcement may inadvertently increase the recurrence of problem behavior in the face of challenges because reinforcers for appropriate behavior occur in the same context as problem behavior. The current study evaluated one potential approach to mitigating these problems with differential reinforcement treatments based on behavioral momentum theory. Specifically, appropriate behavior was trained in contexts without a history of reinforcement prior to intervening with problem behavior. Participants were 4 children with autism spectrum disorder. Treatment used telehealth to implement functional communication training (FCT) in three alternative contexts with minimal or no history of reinforcement for problem behavior before initiating FCT in the treatment context. Evaluations of the effects of treatment and tests of resurgence were conducted intermittently during treatment to evaluate maintenance. When FCT treatment was initiated in alternative contexts, initial results were comparable to more typical implementations of FCT. Resurgence was reduced to similar levels during tests of resurgence for all participants when compared to more typical previously published implementations of FCT, but clinically significant reductions in resurgence occurred more quickly in the present study. These findings support training appropriate behavior in an alternative context to mitigate the resurgence of problem behavior during differential reinforcement treatments.

The Mentoring Program in the Department of Pediatrics, the University of Iowa.

In this article, the mentoring program in Pediatrics for PhD-level behavior analysts at The University of Iowa is described.

A laboratory model for evaluating relapse of undesirable caregiver behavior.

The success of behavioral treatments like functional communication training depends on their continued implementation outside of the clinical context, where failures in caregiver treatment adherence can lead to the relapse of destructive behavior. In the present study, we developed a laboratory model for evaluating the relapse of undesirable caregiver behavior that simulates two common sources of disruption (i.e., changes in context and in treatment efficacy) believed to affect caregiver treatment adherence using simulated confederate destructive behavior. In Phase 1, the caregiver's delivery of reinforcers for destructive behavior terminated confederate destructive behavior in a home-like context. In Phase 2, the caregiver implemented functional communication training in a clinical context in which providing reinforcers for destructive or alternative behavior terminated confederate destructive behavior. In Phase 3, the caregiver returned to the home-like context, and caregiver behavior produced no effect on confederate destructive or alternative behavior, simulating an inconsolable child. Undesirable caregiver behavior relapsed in three of four treatment-adherence challenges.

Effects of response preference on resistance to change.

Treatments based on differential reinforcement of alternative behavior, such as functional communication training, are widely used. Research regarding the maintenance of related treatment effects is limited. Nevin and Wacker (2013) provided a conceptual framework, rooted in behavioral momentum theory, for the study of treatment maintenance that addressed two components: (a) reemergence of problem behavior, and (b) continued expression of appropriate behavior. In the few studies on this topic, focus has been on variables impacting the reemergence of problem behavior, with fewer studies evaluating the persistence of appropriate behavior. Given the findings from applied research related to functional communication training, variables related to response topography, such as response preference, may impact this aspect of maintenance. In the current study, the impact of response preference on persistence was evaluated in the context of functional communication training for individuals who did not exhibit problem behavior (Experiment 1) and for individuals with a history of reinforcement for problem behavior (Experiment 2). High-preferred mands were more persistent than low-preferred mands. These findings suggest that response related variables, such as response preference, impact response persistence and further suggest that response related variables should be considered when developing interventions such as functional communication training.

Managing patients with oncologic complications in the emergency department [digest].

As the prevalence of cancer continues to increase in the general population and improvements in cancer treatment prolong survival, the incidence of patients presenting to the emergency department with oncologic complications will, similarly, continue to rise. This issue reviews 3 of the more common presentations of oncology patients to the emergency department: metastatic spinal cord compression, tumor lysis syndrome, and febrile neutropenia. Signs and symptoms of these conditions can be varied and nonspecific, and may be related to the malignancy itself or to an adverse effect of the cancer treatment. Timely evidence-based decisions in the emergency department regarding diagnostic testing, medications, and arrangement of disposition and oncology follow-up can significantly improve a cancer patient's quality of life. [Points & Pearls is a digest of Emergency Medicine Practice.].

Managing patients with oncologic complications in the emergency department.

As the prevalence of cancer continues to increase in the general population and improvements in cancer treatment prolong survival, the incidence of patients presenting to the emergency department with oncologic complications will, similarly, continue to rise. This issue reviews 3 of the more common presentations of oncology patients to the emergency department: metastatic spinal cord compression, tumor lysis syndrome, and febrile neutropenia. Signs and symptoms of these conditions can be varied and nonspecific, and may be related to the malignancy itself or to an adverse effect of the cancer treatment. Timely evidence-based decisions in the emergency department regarding diagnostic testing, medications, and arrangement of disposition and oncology follow-up can significantly improve a cancer patient's quality of life.