A Non-parametric Analysis of Gender Differences With the Impacts of Applied Behavior Analysis on Autistic Individuals.

Introduction Considering the scarcity of research that directly investigates the differences between genders in their response to applied behavior analysis (ABA) therapy for individuals diagnosed with autism spectrum disorder (ASD), the objective of this study is twofold. First, it aims to reinforce the male-to-female ratio reported in existing scientific literature, thereby contributing to a broader understanding of gender distribution in ABA therapy for ASD. Second, it seeks to identify gender-based differences in aggregate target behaviors at various time intervals using three distinct datasets. The goal is to determine if gender influences the effectiveness of ABA therapy for ASD, which could inform future therapeutic strategies. Ultimately, this study strives to enhance our understanding of gender disparities in ABA therapy response among ASD individuals and hopes to improve therapeutic outcomes for all, regardless of gender. Materials and methods Three to five behavioral technicians per child collected daily general target mastery data for 263 individuals with autism. This data was gathered using a large N design through retrospective chart reviews within the "Catalyst" tracking software (DataFinch Technologies, Atlanta, USA). Three separate datasets were collected from June 7, 2023 to January 7, 2024. Behavior analysts employed a mixed model of discrete trial training, mass trials, and naturalistic environment treatment over seven months. General target mastery data was assembled for 259 children and four adults, with seven data instances missing. Descriptive statistics encompassed central tendency and dispersion measures, including the data distribution's mean, standard deviation, median, and range. Non-parametric inferential analysis was performed with the Mann-Whitney U test. Results Mann-Whitney U computations resulted in non-significant gender differences on all gender comparisons for the three datasets covering the seven-month timeframe. Dataset #1: Time 1-(U=727.5, p=0.846, ή2=0.0002, Time 2-(U=736, p=0.910, ή2=0.00005), Time 3-(U=687.5, p=0.569, ή2=0.001) Dataset #2: Time 1-(U=781, p=0.383, ή2=0.003), Time 2-(U=819.5, p=0.585, ή2=0.001), Time 3-(U=825, p=0.618, ή2=0.001) Dataset #3: Time 1-(U=395, p=0.198, ή2=0.007), Time 2-(U=373.5, p=0.365, ή2 =0.003), Time 3-(U=363, p=0.471, ή2=0.002), Time 4-(U=366.5, p=0.436, ή2 =0.003), Time 5-(U=371, p=0.391, ή2=0.003), Time 6-(U=394, p=0.208, ή2=0.007), Time 7-(U=373, p=0.373, ή2=0.003), Time 8-(U=371.5, p=0.387, ή2=0.003), Time 9-(U=464.5, p=0.512, ή2=0.002), Time 10-(U=356.5, p=0.546, ή2=0.002), Time 11-(U=357.5, p=0.535, ή2=0.002), Time 12-(U=350.5, p=0.346, ή2=0.004) Conclusions This study suggests no significant gender differences in response to ABA therapy among individuals with autism, indicating its potential effectiveness for both genders. However, these findings should be interpreted cautiously due to statistical uncertainties reflected in the broad confidence intervals as they hint at possible substantial gender differences. Further research, including an extension study, must confirm these results and understand potential gender nuances in ABA therapy response. This could help tailor more effective, personalized therapeutic strategies for individuals with autism.

Comparative Effects of Applied Behavior Analysis on Male and Female Individuals With Autism Spectrum Disorder.

Introduction Current evidence-based treatments for autism spectrum disorder (ASD) are based on applied behavior analysis (ABA). However, research on gender differences in ABA therapy response is limited. This study seeks to (1) confirm the 4:1 male-to-female ratio reported in the literature and (2) identify any possible gender differences in target behaviors over seven timepoints measured every two weeks. Materials and methods  For three months, from March 19, 2023, to June 11, 2023, a team of 3-5 behavioral technicians per individual collected daily data on general target mastery for 100 individuals with ASD treated with ABA. Data was collected at seven timepoints every two weeks. Descriptive demographics were computed. Two independent sample t-tests were performed to determine significant or nonsignificant gender differences with the seven timepoint variables.  Results Nonstatistically significant gender differences (p > .05) were found on all seven cumulative target behavior timepoints measured at two-week intervals. For targets mastered Time 1, baseline between males and females, there was no significant difference in the means for males (M = 1.0571, SD = 1.9196) and females (M = 2.0455, SD = 3.9457) (t(90) = -1.591, p = 0.115, confidence interval (CI) = -2.2223, 0.2456, d = -0.389). For targets mastered Time 2, two weeks between males and females, there was no significant difference in the means for males (M = 3.7132; SD = 4.5065) and females (M = 4.0682, SD = 5.1508) (t(88) = -0.310, p = 0.757, CI = -2.6305, 1.92056, d = -0.076). For targets mastered Time 3, four weeks between males and females, there was no significant difference in the means for males (M = 7.0956; SD = 8.7781) and females (M = 8.6136; SD = 11.2799) (t(88) = -0.656, p = 0.514, CI = -6.1173, 3.0811, d = -0.161). For targets mastered Time 4, six weeks between males and females, there was no significant difference in the means for males (M = 13.1728, SD = 16.2003) and females (M = 13.0682, SD = 16.9272) (t(88) = 0.026, p = 0.979, CI = -7.8779, 8.0871, d = 0.006). For targets mastered Time 5, eight weeks between males and females, there was no significant difference in the means for males (M = 17.2096; SD = 18.8546) and females (M = 17.4286, SD = 22.1683) (t(87) = -0.045, p = 0.965, CI = -9.9773, 9.5393, d = -0.011). For targets mastered Time 6, 10 weeks between males and females, there was no significant difference in the means for males (M = 21.0074, SD = 21.3329) and females (M = 20.6818, SD = 26.1231) (t(88) = 0.059, p = 0.953, CI = -10.6752, 11.3262, d = 0.014). For targets mastered Time 7, 12 weeks between males and females, there was no significant difference in the means for males (M = 26.1196, SD = 24.2235) and females (M = 29.6364, SD = 33.7406) (t(89) = -0.536, p = 0.593, CI = -16.5431, 9.5094, d = -0.131). Conclusions The study indicates that ABA treatments may be equally beneficial for both genders with ASD, showing no significant gender differences. However, the broad CIs in this study imply a level of statistical uncertainty, indicating potential gender differences, suggesting the results may not be uniform across genders. These findings challenge assumptions on gender-specific treatment responses, implying that ABA treatments shouldn't be recommended based on gender. Instead, individual needs should guide treatment recommendations. Future research could consider other response moderators like age, ASD severity, or coexisting mental health conditions.

An Internal Consistency Reliability Study of the Catalyst Datafinch Applied Behavior Analysis Data Collection Application With Autistic Individuals.

Introduction Many psychometric studies have scrutinized the dependability of different instruments for evaluating and treating autism using applied behavior analysis (ABA). However, there has been no exploration into the psychometric attributes of the Catalyst Datafinch Applied Behavior Analysis Data Collection Application, namely, internal consistency reliability measures. Materials and methods  Four datasets were extracted (n=100, 98, 103, and 62) from published studies at The Oxford Center, Brighton, MI, ranging from March 19, 2023, through January 8, 2024, using Catalyst Datafinch as the data collection tool. All data were gathered by Board Certified Behavior Analysts (BCBAs) and behavioral technicians and designed to replicate how practitioners collect traditional paper and pencil data. SPSS Statistics (v. 29.0) computed internal consistency reliability measures, including Cronbach's alpha, inter-item, split-half, and interclass correlation coefficients. Results  Dataset #1: Cronbach's alpha was 0.916 with seven items, indicating excellent reliability. Cronbach's split-half reliability for Part 1 was 0.777, indicating good reliability, and for Part 2 was 0.972, indicating excellent reliability. Guttman split-half coefficient was 0.817, indicating good reliability. Inter-item correlation coefficients ranged from 0.474 to 0.970. The average measures interclass correlation (ICC) was 0.916, indicating excellent reliability. Single measures (ICC) reliability was 0.609, indicating acceptable reliability. Dataset #2: Cronbach's alpha was 0.954 with three items, indicating excellent reliability. Cronbach's split-half reliability for Part 1 was 0.912, indicating excellent reliability, and for Part 2 was 0.975, indicating excellent reliability. Guttman split-half coefficient was 0.917, indicating excellent reliability. Inter-item correlation coefficients ranged from 0.827 to 0.977. Average measures (ICC) was 0.954, indicating excellent reliability. Single measures (ICC) reliability was 0.875, indicating good reliability. Dataset #3: Cronbach's alpha was 0.974 with three items, indicating excellent reliability. Cronbach's split-half reliability for Part 1 was 0.978, indicating excellent reliability. Split-half reliability for Part 2 was 0.970, indicating excellent reliability. Guttman split-half coefficient was 0.935, indicating excellent reliability. Inter-item correlation coefficients ranged from 0.931 to 0.972. The average measures (ICC) was 0.974, indicating excellent reliability. Single measures (ICC) reliability was 0.926, indicating excellent reliability. Dataset #4: Cronbach's alpha was 0.980 with 12 items, indicating excellent reliability. Cronbach's split-half reliability for Part 1 was 0.973, indicating excellent reliability. Split-half reliability for Part 2 was 0.996, indicating excellent reliability. Guttman split-half coefficient was 0.838, indicating good reliability. Inter-item correlation coefficients ranged from 0.692 to 0.999. The average measures (ICC) was 0.980, indicating excellent reliability. Single measures (ICC) reliability was 0.804, indicating good reliability. Conclusions These results suggest that Catalyst Datafinch demonstrates high internal consistency reliability when used with individuals with autism. This indicates that the application is reliable for collecting and analyzing behavioral data in this population. The ratings ranged from good to excellent, indicating a high consistency in the measurements.

The Effects of Applied Behavior Analysis on Verbal Behavior With Autistic Individuals Using the Verbal Behavior Milestones Assessment and Placement Program (VBMAPP) and the Assessment of Basic Language and Learning Skills (ABLLS).

Introduction  Applied behavior analysis (ABA) is a fundamental practice-based intervention for treating autism spectrum disorder (ASD). Few studies have directly measured and evaluated the effects of ABA on verbal behaviors, mainly using the Verbal Behavior Milestones Assessment and Placement Program (VBMAPP) and the Assessment of Basic Language and Learning Skills (ABLLS) as outcome measures. This study aims to fill this gap by examining the relationship between ABA interventions and the enhancement of verbal skills, as measured by the VBMAPP and the ABLLS, in a convenience sample of individuals with ASD.  Materials and methods At The Oxford Centers (TOCs) in Brighton and Troy, Michigan, USA, 33 individuals with autism received treatment from January 2018 to July 2021, spanning 43 months. A pretest-posttest design was employed to retrospectively examine any impacts between ABA interventions and alterations in verbal scores among individuals with ASD. Depending on developmental age, all subjects underwent two verbal assessments with a six-month interval in-between. Twelve children were administered the VBMAPP, while 21 were given the ABLLS. Results Paired t-tests for pretest and posttest VBMAPP subscales resulted in statistically significant effects (p<0.05) for (VBMAPP - Mand), (VBMAPP - Tact), (VBMAPP - Listener Responding), (VBMAPP - Visual Perceptual Skills and Matching-to-Sample), (VBMAPP -Independent Play), (VBMAPP - Social Play), (VBMAPP - Motor Imitation), (VBMAPP - Spontaneous Vocalization), (VBMAPP - Intraverbal), (VBMAPP - Group Behavior), and (VBMAPP - Linguistic Structure). As measured by Cohen's d, effect sizes were moderate to mostly high (-0.623 to -1.688). There were non-significant results (p>0.05) for (VBMAPP - Listener Responding by Feature, Function, and Class) and (VBMAPP - Echoic). Paired t-tests for pretest and posttest ABLLS subscales resulted in statistically significant effects (p<.05) for all ABLLS scales: (ABLLS - Receptive Language), (ABLLS - Requests), (ABLLS - Labeling), (ABLLS - Intraverbals), (ABLLS - Spontaneous Vocalizations), (ABLLS - Syntax Grammar), (ABLLS - Social Interactions), and (ABLLS - Generalized Responding). As measured by Cohen's d, effect sizes were moderate to mostly high (-0.656 to -1.372). Conclusions  The administration of ABA treatments had a noteworthy influence, with statistically significant impacts on improving verbal behaviors on 11 of the 13 VBMAPP scales and all of the ABLLS scales. As measured by Cohen's d, effect sizes were moderate to high for both scales. These findings underscore the importance and effectiveness of ABA interventions in enhancing verbal skills in children with ASD. However, it's crucial to note that further confirmatory studies are required to verify the reliability of these original findings, emphasizing the ongoing need for research in this field.

A Descriptive Study on the Impacts of Hyperbaric Oxygen Therapy on Autistic Individuals Using Parent Testimonies.

Introduction Hyperbaric oxygen therapy (HBOT) has been influential in treating many physical and psychological ailments, including the symptoms of autism. This current study aims to evaluate HBOT parents' goals and exit interviews describing the positive, negative, or no impacts experienced from the HBOT dives, asking the question, "Are your child's symptoms improving?" Methods Between January 2020 and July 2023, a Class B monoplace hyperbaric chamber (Sechrist 3300H, Sechrist Industries, Inc., Anaheim, California, United States) was used to administer HBOT sessions to patients with autism. Medical-grade oxygen was pressurized to 1.5-2.0 atmospheres absolute at a rate of 1-2 psi/min, with an average oxygen percentage of 100%, for up to five sessions per week. Retrospective descriptive data and patient information through parent testimonials were collected through a chart review of 30 children and one adult with autism who experienced HBOT sessions. Data were presented through exit interviews describing how parents felt about their child's progress toward goals. Four raters rated parent testimonies on a 5-point Likert scale (1 = Much worse, 2 = Somewhat worse, 3 = Stayed the same, 4 = Somewhat improved, and 5 = Much improved), and an inter-rater reliability estimate using interclass correlation (2) (r = 0.831) was derived, indicating excellent agreement between raters. Results Parents/caregivers provided testimony in an exit interview with a registered nurse after the individual with autism received an entire course of HBOT dives. Descriptive statistics resulted in Rater #1 (M = 4.19, median = 4, SD = 0.654): 87.1% of Rater #1 ratings were Somewhat improved and Much improved; Rater #2 (M = 4.23, median = 4, SD = 0.717): 83.9% of Rater #2 ratings were Somewhat improved and Much improved; Rater #3 (M = 4.23, median = 4, SD = 0.560): 93.5% of Rater #3 ratings were Somewhat improved and Much improved; and Rater #4 (M = 4.26, median = 4, SD = 0.631): 90.3% of Rater #4 ratings were Somewhat improved and Much improved. One-way ANOVA resulted in F (3,123) = 0.052, p = 0.984, which indicated a nonstatistically significant mean difference between rater groups. Conclusions The current study assessed HBOT parents'/caregivers' goals and exit interviews, describing the effects experienced from the complete course of HBOT dives on their children/individuals. A majority of parents/caregivers declared that their condition had "Much improved" or "Somewhat improved," based on the 5-point Likert scale. Based on parents'/caregivers' testimonies, HBOT was demonstrated as a safe and effective intervention, and side effects were primarily mild and did not lead to treatment discontinuation. As a result of this analysis, we recommend continued use of HBOT for treatment.

Examining the Effects of Discrete Trials, Mass Trials, and Naturalistic Environment Training on Autistic Individuals Using Repeated Measures.

INTRODUCTION: Behavioral interventions based on applied behavior analysis (ABA) form current evidence-based practices in treating autism spectrum disorder (ASD). Research is scarce relative to the broad effects of intensive repetitive, discrete trial training, and mass trials combined with a naturalistic environment as measured by overall general target behaviors. The primary objective of this study was to evaluate the effectiveness of a mixed behavioral model consisting of discrete trial training and mass trial interventions in the naturalistic environment, using a repeated measures design with a retrospective snapshot cohort of 93 individuals with autism. METHODS: A repeated measures analysis tracked 89 autistic children with four adult autistic individuals over seven time points during a three-month snapshot period from March 19, 2023, to June 11, 2023. This study determined the effectiveness of applied behavior analysis (ABA) interventions combining discrete trial training, mass trials, and naturalistic environment training on mastered broad target behaviors in autistic individuals using a mixed (between and within) ANOVA statistical design. RESULTS: Mixed (between and within) ANOVA indicated overall statistical significance, F (6,674)=45.447, p<0.001, partial eta squared=0.365 across time. These results indicated a large effect size. Multiple comparisons showed statistical significance (p<0.001) on all 21 multiple comparisons between timepoints. There was also a significant interaction effect with time × age category, F (24,474)=2.961, p<0.001, partial eta squared=0.130. These results also indicated a large effect size. CONCLUSIONS: Autistic individuals who received applied behavior analysis combining discrete trial training, mass trials, and naturalistic environment training intervention demonstrated statistically significant improvement in target behaviors over the three-month snapshot period, the most prominent being in the 13-16 years age category.

The Effects of Hyperbaric Oxygen Treatment on Verbal Scores in Children With Autism Spectrum Disorder: A Retrospective Trial.

Introduction Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects millions worldwide. Suggested pathophysiology includes cerebral hypoperfusion, inflammation, mitochondrial and immune dysregulation, and oxidative stress. Debate exists concerning the benefit of hyperbaric oxygen therapy (HBOT) in treating ASD and its impacts on verbal behavior. The present study directly assesses the impacts of HBOT treatments on verbal behavior using a novel and unique manner.  Materials and methods A two-group quasi-experimental trial using a pretest and a posttest was designed to retrospectively assess (n = 65) any association between HBOT and change in verbal scores in children (n = 65) with ASD. All children completed two verbal tests six months apart, either the Verbal Behavior Milestones Assessment and Placement Program (VBMAPP) or the Assessment of Basic Language and Learning Skills (ABLLS), based on their developmental age. The control cohort received applied behavior analysis (ABA) without HBOT. The experimental cohort received ABA and a minimum of 40 HBOT treatments, breathing 100% oxygen at 2.0 atmosphere absolute (ATA) for 60 minutes. Results Sixty-five children were included, of which 32 received HBOT (mean (M) = 5.1, standard deviation (SD) = 2.93), with an age range of two to 17 years. More than 63% of the subjects had an autism severity level of three. The 23 children administered VBMAPP who received HBOT showed substantial mean differences with high effect sizes (ESs) (-0.743 to -1.65) and a total score (TS) ES equal to -1.23 as measured by Cohen's d. There was a statistically significant improvement (p < 0.05) in all VBMAPP milestone domains and TS. TS change from baseline versus those in the non-HBOT (Control-ABA) group (n=12) was 46.41 ± 20.14 vs 14.42 ± 6.99; p < 0.0001, ES = -1.23. The 30 children administered the ABLLS showed substantial mean difference (TS) change from baseline 268.89 ± 182.05 vs 190.81 ± 135.26 and exhibited small to medium (-.114 to -.773) ESs with a TS ES = -0.487. Due to the high within-group variability (low statistical power) within the ABLLS cohort, there was a non-significant mean difference between the control (ABA) and experimental (ABA + HBO2) groups' difference scores (p > 0.2024), despite the medium (TS) ES. Conclusions The child cohorts administered the VBMAPP and the ABLLS demonstrated substantial improvements between the non-HBOT (control-ABA) and HBOT (experimental-ABA + HBO2) groups as measured by the significant mean differences and small to large ESs. Simply put, the children in the experimental cohort acquired more verbal skills than their counterparts in the control group.

The salivary microbiota of patients with acute lower respiratory tract infection-A multicenter cohort study.

The human microbiome contributes to health and disease, but the oral microbiota is understudied relative to the gut microbiota. The salivary microbiota is easily accessible, underexplored, and may provide insight into response to infections. We sought to determine the composition, association with clinical features, and heterogeneity of the salivary microbiota in patients with acute lower respiratory tract infection (LRTI). We conducted a multicenter prospective cohort study of 147 adults with acute LRTI presenting to the emergency department of seven hospitals in three states (Pennsylvania, Michigan, and Ohio) between May 2017 and November 2018. Salivary samples were collected in the emergency department, at days 2-5 if hospitalized, and at day 30, as well as fecal samples if patients were willing. We compared salivary microbiota profiles from patients to those of healthy adult volunteers by sequencing and analyzing bacterial 16-rRNA. Compared to healthy volunteers, the salivary microbiota of patients with LRTI was highly distinct and strongly enriched with intestinal anaerobes such as Bacteroidaceae, Ruminococcaceae, and Lachnospiraceae (e.g., mean 10% relative abundance of Bacteroides vs < 1% in healthy volunteers). Within the LRTI population, COPD exacerbation was associated with altered salivary microbiota composition compared to other LRTI conditions. The largest determinant of microbiota variation within the LRTI population was geography (city in which the hospital was located).

Stress-level glucocorticoids increase fasting hunger and decrease cerebral blood flow in regions regulating eating.

CONTEXT: The neural regulation of appetite and energy homeostasis significantly overlaps with the neurobiology of stress. Frequent exposure to repeated acute stressors may cause increased allostatic load and subsequent dysregulation of the cortico-limbic striatal system leading to inefficient integration of postprandial homeostatic and hedonic signals. It is therefore important to understand the neural mechanisms by which stress generates alterations in appetite that may drive weight gain. OBJECTIVE: To determine glucocorticoid effects on metabolic, neural and behavioral factors that may underlie the association between glucocorticoids, appetite and obesity risk. METHODS: A randomized double-blind cross-over design of overnight infusion of hydrocortisone or saline followed by a fasting morning perfusion magnetic resonance imaging to assess regional cerebral blood flow (CBF) was completed. Visual Analog Scale (VAS) hunger, cortisol and metabolic hormones were also measured. RESULTS: Hydrocortisone relative to saline significantly decreased whole brain voxel based CBF responses in the hypothalamus and related cortico-striatal-limbic regions. Hydrocortisone significantly increased hunger VAS pre-scan, insulin, glucose and leptin, but not other metabolic hormones versus saline CBF groups. Hydrocortisone related increases in hunger were predicted by less reduction of CBF (hydrocortisone minus saline) in the medial OFC, medial brainstem and thalamus, left primary sensory cortex and right superior and medial temporal gyrus. Hunger ratings were also positively associated with plasma insulin on hydrocortisone but not saline day. CONCLUSIONS: Increased glucocorticoids at levels akin to those experienced during psychological stress, result in increased fasting hunger and decreased regional cerebral blood flow in a distinct brain network of prefrontal, emotional, reward, motivation, sensory and homeostatic regions that underlie control of food intake.

A Detroit Student-Run Free Clinic's Management of Select Chronic Diseases.

AIM: The Cass Clinic is a student-run free clinic in Detroit, Michigan that treats chronic diseases including hypertension (HTN), diabetes mellitus (DM), and obesity. Our study aims to quantify the effectiveness of our clinic in managing chronic diseases. SUBJECT AND METHODS: This study assessed selected health outcomes for 137 patients who visited our clinic between September 1, 2017 and August 31, 2018 based on initial and most recent surrogate markers including manual blood pressure, hemoglobin A1c (HbA1c), and body mass index (BMI) recorded in the clinic's medical record system dating back to 2012. RESULTS: Patients were divided into two groups: occasionally seen patients (OSP) and frequently seen patients (FSP). FSP with HTN had systolic blood pressure (SBP) decreased by an average of 14.1 mmHg and diastolic blood pressure (DBP) decreased by 9.8 mmHg, which were statistically associated with the number of clinic visits. Additionally, all patients treated at Cass Clinic saw a decrease in their HbA1c and BMI. HbA1c in OSP decreased by 0.50%. HbA1c in the FSP decreased by 1.7%. Patients with at least two recorded BMIs (n=73) saw a decrease of 0.13 kg/m2. CONCLUSION: The data from our analysis support that a student-run free clinic model like Cass Clinic provides long-term value for patients who frequently utilize the clinic. These clinics also act as an important resource for the community by making positive strides toward better health in multiple measurable outcomes, including HTN and DM management.

Early echocardiographic assessment of cardiac function may be prognostically informative in unresuscitated patients with sepsis: A prospective observational study.

PURPOSE: The goal of this study was to explore the association cardiac function at Emergency Department (ED) presentation prior to the initiation of resuscitation, and its change at 3-hours, with adverse outcomes in patients with sepsis. METHODS: This was a prospective observational study of patients presenting to an urban ED with suspected sepsis. Patients had a point-of-care echocardiogram performed prior to initiation of resuscitation and again 3 hours later. Left-ventricular (LV) parameters recorded included e', and E/e', and ejection fraction (EF); right-ventricular (RV) function was evaluated using tricuspid annular plane systolic excursion (TAPSE). Logistic and generalized linear regression were used to assess the association of echocardiographic parameters and ≥ 2-point increase in SOFA score at 24 hours (primary outcome) and 24-hours SOFA score and in-hospital mortality (secondary outcomes). RESULTS: For ΔSOFA ≥ 2 and 24-hour SOFA score, declining LVEF was associated with better outcomes in patients with greater baseline SOFA scores, but worse outcomes in patients with lower baseline scores. A similar relationship was found for ΔTAPSE at 3 hours. Reduced LVEF at presentation was associated with increased mortality after adjusting for ED SOFA score (odds-ratio (OR) 0.76 (CI 0.60-0.96). No relationship between diastolic parameters and outcomes was found. IVF administration was similar across ΔLVEF/TAPSE sub-groups. CONCLUSIONS: Our results suggest that early change in LV and RV systolic function are independently prognostic of sepsis illness severity at 24-hours. Further study is needed to determine if this information can be used to guide treatment and improve outcomes.

Increasing illness severity is associated with global myocardial dysfunction in the first 24 hours of sepsis admission.

BACKGROUND: Septic cardiomyopathy was recognized more than 30 years ago, but the early phase remains uncharacterized as no existing studies captured patients at the time of Emergency Department (ED) presentation, prior to resuscitation. Therapeutic interventions alter cardiac function, thereby distorting the relationship with disease severity and outcomes. The goal of this study was to assess the impact of illness severity on cardiac function during the first 24 h of sepsis admission. METHODS: This was a pre-planned secondary analysis of a prospective observational study of adults presenting to the ED with suspected sepsis (treatment for infection plus either lactate > 2 mmol/liter or systolic blood pressure < 90 mm/Hg) who received < 1L IV fluid before enrollment. Patients had 3 echocardiograms performed (presentation, 3, and 24 h). The primary outcome was the effect of increasing sepsis illness severity, defined by ED Sequential Organ Failure Assessment (SOFA) score, on parameters of cardiac function, assessed using linear mixed-effects models. The secondary goal was to determine whether cardiac function differed between survivors and non-survivors, also using mixed-effects models. RESULTS: We enrolled 73 patients with a mean age of 60 (SD 16.1) years and in-hospital mortality of 23%. For the primary analysis, we found that increasing ED SOFA score was associated with worse cardiac function over the first 24 h across all assessed parameters of left-ventricular systolic and diastolic function as well as right-ventricular systolic function. While baseline strain and E/e' were better in survivors, in the mixed models analysis, the trajectory of Global Longitudinal Strain and septal E/e' over the first 24 h of illness differed between survivors and non-survivors, with improved function at 24 h in non-survivors. CONCLUSIONS: In the first study to capture patients prior to the initiation of resuscitation, we found a direct relationship between sepsis severity and global myocardial dysfunction. Future studies are needed to confirm these results, to identify myocardial depressants, and to investigate the link with adverse outcomes so that therapeutic interventions can be developed.

Effect of P2Y12 Inhibitors on Survival Free of Organ Support Among Non-Critically Ill Hospitalized Patients With COVID-19: A Randomized Clinical Trial.

Importance: Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19. Objective: To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021. Interventions: Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n = 293) or a therapeutic dose of heparin only (usual care) (n = 269) in a 1:1 ratio for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures: The composite primary outcome was organ support-free days evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalization (range, -1 to 21 days; higher scores indicate less organ support and better outcomes). The primary safety outcome was major bleeding by 28 days as defined by the International Society on Thrombosis and Hemostasis. Results: Enrollment of non-critically ill patients was discontinued when the prespecified criterion for futility was met. All 562 patients who were randomized (mean age, 52.7 [SD, 13.5] years; 41.5% women) completed the trial and 87% received a therapeutic dose of heparin by the end of study day 1. In the P2Y12 inhibitor group, ticagrelor was used in 63% of patients and clopidogrel in 37%. The median number of organ support-free days was 21 days (IQR, 20-21 days) among patients in the P2Y12 inhibitor group and was 21 days (IQR, 21-21 days) in the usual care group (adjusted odds ratio, 0.83 [95% credible interval, 0.55-1.25]; posterior probability of futility [defined as an odds ratio <1.2], 96%). Major bleeding occurred in 6 patients (2.0%) in the P2Y12 inhibitor group and in 2 patients (0.7%) in the usual care group (adjusted odds ratio, 3.31 [95% CI, 0.64-17.2]; P = .15). Conclusions and Relevance: Among non-critically ill patients hospitalized for COVID-19, the use of a P2Y12 inhibitor in addition to a therapeutic dose of heparin, compared with a therapeutic dose of heparin only, did not result in an increased odds of improvement in organ support-free days within 21 days during hospitalization. Trial Registration: ClinicalTrials.gov Identifier: NCT04505774.

Do septic patients with reduced left ventricular ejection fraction require a low-volume resuscitative strategy?

BACKGROUND: Many clinicians are wary of administering 30 cc/kg of intravenous fluid (IVF) to septic patients with reduced left-ventricular ejection fraction (rLVEF), fearing volume overload. Prior studies have used history of heart failure, rather than LVEF measured at presentation, thereby potentially distorting the relationship between rLVEF, IVF, and adverse outcomes. Our goal was to assess the relationship between IVF volume and outcomes in patients with, versus without, rLVEF. METHODS: This was a prospective observational study performed at an urban Emergency Department (ED). Included patients were adults with suspected sepsis, defined as being treated for infection plus either systolic blood pressure <90 mm/Hg or lactate >2 mmol/L. All patients had LVEF assessed by ED echocardiogram, prior to receipt of >1 l IVF. MEASUREMENTS AND MAIN RESULTS: We enrolled 73 patients, of whom 33 had rLVEF, defined as <40%. Patients with rLVEF were older, had greater initial lactate, more ICU admission, and more vasopressor use. IVF volume was similar between LVEF groups at 3-h (2.2 (IQR 0.8) vs 2.0 (IQR 2.4) liters) while patients with rLVEF were more likely to achieve 30 cc/kg (61% (CI 44-75) vs 45% (CI 31-60). In the reduced versus not-reduced LVEF groups, hospital days, ICU days, and ventilator days were similar: 8 (IQR 7) vs 6.5 (8.5) days, 7 (IQR 7) vs 5 (4) days, and 4 (IQR 8) vs. 5 (10) days, respectively. CONCLUSIONS: Septic patients with rLVEF at presentation received similar volume of IVF as those without rLVEF, without an increase in adverse outcomes attributable to volume overload. While validation is needed, our results suggest that limiting IVF administration in the setting of rLVEF is not necessary.

Expanded Analysis of 20 Pneumococcal Serotypes Associated With Radiographically Confirmed Community-acquired Pneumonia in Hospitalized US Adults.

BACKGROUND: Streptococcus pneumoniae is a causative agent of community-acquired pneumonia (CAP). The 13-valent pneumococcal conjugate vaccine (PCV13) has significantly decreased the burden of PCV13-serotype pneumococcal disease; however, disease from nonvaccine serotypes remains substantial. A recent study documented the persistence of PCV13 serotypes among US adults hospitalized with radiographically confirmed CAP. The current analysis used a recently developed urinary antigen detection (UAD) assay (UAD2) to extend these results to additional serotypes included in an investigational PCV20 vaccine. METHODS: This prospective study enrolled adults aged ≥18 years hospitalized with radiographically confirmed CAP between October 2013 and September 2016. Presence of S pneumoniae was determined by blood and respiratory sample culture, BinaxNOW urine testing, and UAD. In addition to Quellung on cultured isolates when available, serotypes were identified from urine specimens using UAD1 for PCV13 serotypes and UAD2 for 7 PCV20-unique serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) and 4 additional serotypes (2, 9N, 17F, and 20). RESULTS: Among 12 055 subjects with radiographically confirmed CAP, 1482 were positive for S pneumoniae. PCV13- and PCV20-unique serotypes were associated with 37.7% (n = 559) and 27.0% (n = 400) of cases, respectively; 288 subjects were exclusively diagnosed as positive for S pneumoniae by UAD2. Demographic and clinical disease characteristics were similar between subjects with CAP caused by PCV13 and PCV20-unique serotypes. CONCLUSIONS: The current analysis using UAD2 identified a sizeable proportion of hospitalized adult CAP associated with PCV20-unique serotypes. PCV20 may therefore address the burden of CAP caused by the additional serotypes present in the vaccine.

Elevated COVID19 mortality risk in detroit area hospitals among patients from census tracts with extreme socioeconomic vulnerability.

BACKGROUND: the incidence of novel coronavirus disease (COVID19) is elevated in areas with heightened socioeconomic vulnerability. Early reports from US hospitals also implicated social disadvantage and chronic disease history as COVID19 mortality risk factors. However, the relationship between race and COVID19 mortality remains unclear. METHODS: we examined in-hospital COVID19 mortality risk factors in a multi-hospital tertiary health care system that serves greater Detroit, Michigan, a predominantly African American city with high rates of poverty and chronic disease. Consecutive adult patients who presented to emergency departments and tested positive for COVID19 from 3/11/2020 through 4/18/2020 were included. Using log-binomial regression, we assessed the relationship between in-hospital mortality and residence in census tracts that were flagged for extreme socioeconomic vulnerability, patient-level demographics, and clinical comorbidities. FINDINGS: a total of 1,015 adults tested positive for COVID19 during the study period; 80% identified as Black people, 52% were male and 53% were ≥ 65 years of age. The median body mass index was 30•4 and the median Charlson Comorbidity Index score was 4. Patients from census tracts that were flagged for vulnerability related to socioeconomic status had a higher mortality rate than their peers who resided in less vulnerable census tracts (ß 0.26, standard error (SE) 0.11, degrees of freedom (df) 378, t-value (t) 2.27, exp(ß) 1.29, p-value 0.02). Adjustment for age category, Black race, sex and/or the Charlson Comorbidity Index score category reduced the magnitude of association by less than 10% [exp(ß) 1.29 vs. 1.21]. Black race [p = 0.38] and sex [p = 0.62] were not associated with mortality in this sample. INTERPRETATION: people who lived in areas flagged for extreme socioeconomic vulnerability had elevated mortality risk in our predominantly African-American cohort of COVID19 patients who were able to seek hospital care during the so-called 'first wave' of the pandemic. By contrast, Black race was not associated with mortality in our sample.

Serial use of existing clinical decisions aids can reduce computed tomography pulmonary angiography for pulmonary embolism.

Pulmonary embolism (PE) remains a diagnostic challenge in emergency medicine. Clinical decision aids (CDAs) like the Pulmonary Embolism Rule-Out Criteria (PERC) are sensitive but poorly specific; serial CDA use may improve specificity. The goal of this before-and-after study was to determine if serial use of existing CDAs in a novel diagnostic algorithm safely decreases the use of CT pulmonary angiograms (CTPA). This was a retrospective before-and-after study conducted at an urban ED with 105,000 annual visits. Our algorithm uses PERC, Wells' score, and D-dimer in series, before moving to CTPA. The algorithm was introduced in January, 2017. Use of CDAs and D-dimer in the 24 months pre- and 12 months post-intervention were obtained by chart review. The algorithm's effect on CTPA ordering was assessed by comparing volume 5 years pre- and 3 years post-intervention, adjusted for ED volume. Mean CTPAs per 1000 adult ED visits was 11.1 in the 5 pre-intervention years and 9.9 in the 3 post-intervention years (p < 0.0001). Use of PERC, Wells' score and D-dimer increased from 1.1%, 1.1%, and 28% to 8.8% (p = 0.0002) 8.1% (p = 0.0005), and 35% (p = 0.0066), respectively. Pre-intervention, there were six potentially missed PEs compared to three in the post-intervention period. Introduction of our serial CDA diagnostic algorithm was associated with increased use of CDAs and D-dimer and reduced CTPA rate without an apparent increase in the number of missed PEs. Prospective validation is needed to confirm these results.

Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial.

IMPORTANCE: The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock. OBJECTIVE: To determine whether the combination of ascorbic acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS: Randomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019. INTERVENTIONS: Patients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102). MAIN OUTCOMES AND MEASURES: The primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses. RESULTS: Among 205 randomized patients (mean age, 68 [SD, 15] years; 90 [44%] women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 [-4.7] points with intervention vs 9.2 to 5.1 [-4.1] points with placebo; adjusted mean difference, -0.8; 95% CI, -1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, -0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively). CONCLUSIONS AND RELEVANCE: In patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03389555.

Body Mass Index and Age Effects on Brain 11ß-Hydroxysteroid Dehydrogenase Type 1: a Positron Emission Tomography Study.

CONTEXT: Cortisol, a glucocorticoid steroid stress hormone, is primarily responsible for stimulating gluconeogenesis in the liver and promoting adipocyte differentiation and maturation. Prolonged excess cortisol leads to visceral adiposity, insulin resistance, hyperglycemia, memory dysfunction, cognitive impairment, and more severe Alzheimer's disease phenotypes. The intracellular enzyme 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) catalyzes the conversion of inactive cortisone to active cortisol; yet the amount of 11ß-HSD1 in the brain has not been quantified directly in vivo. OBJECTIVE: We analyzed positron emission tomography (PET) scans with an 11ß-HSD1 inhibitor radioligand in twenty-eight individuals (23 M/5F): 10 lean, 13 overweight, and 5 obese individuals. Each individual underwent PET imaging on the high-resolution research tomograph PET scanner after injection of 11C-AS2471907 (n = 17) or 18F-AS2471907 (n = 11). Injected activity and mass doses were 246 ± 130 MBq and 0.036 ± 0.039 µg, respectively, for 11C-AS2471907, and 92 ± 15 MBq and 0.001 ± 0.001 µg for 18F-AS2471907. Correlations of mean whole brain and regional distribution volume (VT) with body mass index (BMI) and age were performed with a linear regression model. RESULTS: Significant correlations of whole brain mean VT with BMI and age (VT = 15.23-0.63 × BMI + 0.27 × Age, p = 0.001) were revealed. Age-adjusted mean whole brain VT values were significantly lower in obese individuals. Post hoc region specific analyses revealed significantly reduced mean VT values in the thalamus (lean vs. overweight and lean vs. obese individuals). Caudate, hypothalamus, parietal lobe, and putamen also showed lower VT value in obese vs. lean individuals. A significant age-associated increase of 2.7 mL/cm3 per decade was seen in BMI-corrected mean whole brain VT values. CONCLUSIONS: In vivo PET imaging demonstrated, for the first time, correlation of higher BMI (obesity) with lower levels of the enzyme 11ß-HSD1 in the brain and correlation of increased 11ß-HSD1 levels in the brain with advancing age.