Pulmonary function as a continuum of risk: critical care utilization and survival after allogeneic hematopoietic stem cell transplantation - a multicenter cohort study.

Abnormal pre-transplant pulmonary function tests (PFTs) are associated with reduced survival after allogeneic HCT. Existing scoring systems consider risk dichotomously, attributing risk only to those with abnormal lung function. In a multicenter cohort of 1717 allo-HCT recipients, we examined the association between pre-transplant PFT measures and need for ICU admission (120d), frequency of mechanical ventilation (120d) and overall survival (5 y). Predictive models were developed and validated using Cox proportional hazards, incorporating age, FEV1 (forced expiratory volume in 1-second) and diffusing capacity (DLCO). In univariate analysis, hazard ratios for each outcome (95% CI) were: mechanical ventilation (FEV1: 0.60 [0.52-0.69], DLCO: 0.69 [0.61-0.77], p < 0.001), ICU admission (FEV1: 0.74 [0.67-0.82], DLCO: 0.79 [0.72-0.86], p < 0.001) and overall survival (FEV1: HR 0.87 [0.81-0.94], DLCO: 0.83 [0.77-0.89], p < 0.001). A multivariable Cox model was developed and compared to the HCT-CI Pulmonary score in a validation cohort. This model was better at predicting need for ICU admission and mechanical ventilation, while both models predicted overall survival (p < 0.001). In conclusion, the risk conferred by pre-transplant pulmonary function should be considered in a continuous rather than dichotomous manner. A more granular prognostication system can better inform risk of critical care utilization in the early post-HCT period.

Lung Injury Prediction Model in Bone Marrow Transplantation: A Multicenter Cohort Study.

Rationale: Pulmonary complications contribute significantly to nonrelapse mortality following hematopoietic stem cell transplantation (HCT). Identifying patients at high risk can help enroll such patients into clinical studies to better understand, prevent, and treat posttransplantation respiratory failure syndromes. Objectives: To develop and validate a prediction model to identify those at increased risk of acute respiratory failure after HCT. Methods: Patients underwent HCT between January 1, 2019, and December 31, 2021, at one of three institutions. Those treated in Rochester, MN, formed the derivation cohort, and those treated in Scottsdale, AZ, or Jacksonville, FL, formed the validation cohort. The primary outcome was the development of acute respiratory distress syndrome (ARDS), with secondary outcomes including the need for invasive mechanical ventilation (IMV) and/or noninvasive ventilation (NIV). Predictors were based on prior case-control studies. Measurements and Main Results: Of 2,450 patients undergoing stem cell transplantation, there were 1,718 hospitalizations (888 patients) in the training cohort and 1,005 hospitalizations (470 patients) in the test cohort. A 22-point model was developed, with 11 points from prehospital predictors and 11 points from posttransplantation or early (<24-h) in-hospital predictors. The model performed well in predicting ARDS (C-statistic, 0.905; 95% confidence interval [CI], 0.870-0.941) and the need for IMV and/or NIV (C-statistic, 0.863; 95% CI, 0.828-0.898). The test cohort differed markedly in demographic, medical, and hematologic characteristics. The model also performed well in this setting in predicting ARDS (C-statistic, 0.841; 95% CI, 0.782-0.900) and the need for IMV and/or NIV (C-statistic, 0.872; 95% CI, 0.831-0.914). Conclusions: A novel prediction model incorporating data elements from the pretransplantation, posttransplantation, and early in-hospital domains can reliably predict the development of post-HCT acute respiratory failure.

Social problems in young children: the interplay of ADHD symptoms and facial emotion recognition.

Facial emotion recognition (FER) deficits interfere with interpretation of social situations and selection of appropriate responses. Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms are independently associated with social difficulties and might exacerbate the influence of deficient FER, because children with ADHD symptoms have fewer compensatory resources in social situations when they misinterpret emotions. Very few studies have tested this hypothesis in a community context, where child ADHD symptoms vary on a continuum. The current study extended this work by utilising a community sample (N = 87) of boys and girls in middle childhood (M = 7.83 years) and testing for moderation of FER effects separately by ADHD symptom type (ADHD-I = inattentive, H = hyperactive/impulsive, C = combined) using linear regression. While lower FER was associated with more social problems, this relationship was qualified by the presence of ADHD symptoms. Specifically, only children with relatively high ADHD symptoms in our community sample showed this inverse relationship, which was clearest among children with elevated ADHD-C or ADHD-I symptoms. No gender differences were observed. These results support our primary hypothesis, extend prior findings to boys and girls in the community, and have implications for understanding how ADHD symptoms and FER influence youth social deficits.

Facial Affect Sensitivity Training for Young Children with Emerging CU Traits: An Experimental Therapeutics Approach.

OBJECTIVE: This article delineates best practices in the application of the experimental therapeutics framework for evaluating interventions within the context of randomized controlled trials (RCTs), offering a methodological primer and guiding framework for this approach. We illustrate these practices using an ongoing clinical trial conducted within the framework of a National Institute of Mental Health exploratory phased-innovation award for the development of psychosocial therapeutic interventions for mental disorders (R61/R33), describing the implementation of a novel "Facial Affect Sensitivity Training" (FAST) intervention for children with callous-unemotional (CU) traits. CU traits (e.g., lack of guilt or remorse, low empathy, shallow affect) are an established risk factor for persistent and severe youth misconduct, which reflect impairment in identified neurocognitive mechanisms that interfere with child socialization, and predict poor treatment outcomes, even with well-established treatments for disruptive behavior. METHOD: We outline the stages, goals, and best practices for an experimental therapeutics framework. In the FAST trial, we assert that impaired sensitivity for emotional distress cues (fear and/or sadness) is mechanistically linked to CU traits in children, and that by targeting sensitivity to facial affect directly via a computerized automated feedback and incentive system, we can exert downstream effects on CU traits. RESULTS: In the context of an open pilot trial, we found preliminary support for feasibility and mechanism engagement using FAST. CONCLUSIONS: We summarize pilot study limitations and how they are being addressed in the R61/R33 RCTs, as well as challenges and future directions for psychosocial experimental therapeutics.

The Impact of Alcohol in Inflammatory Bowel Diseases.

Several environmental factors have been implicated in the pathogenesis of inflammatory bowel diseases (IBD); however, the evidence for alcohol is sparse, as is its implications on disease activity and overall management. Here, we examine the available evidence for the effect of alcohol on IBD, including its association with the development of IBD, role in exacerbations, and potential medication interactions. Several mechanisms have been demonstrated to mediate the effects of ethanol in the gastrointestinal tract. Alcohol has been shown to alter the gut microbiome, disrupt intestinal barrier, and increase intestinal permeability, directly and indirectly promoting immune activation. Conversely, specific alcoholic beverages, notably red wine, may have anti-inflammatory properties capable of assisting in disease control and affecting disease monitoring. Nonetheless, most alcohol-mediated effects seem to facilitate intestinal inflammation and consequently impact disease onset, recurrence, and symptom control. Furthermore, alcohol use interferes with the metabolism of several medications leading to increased side effect profiles or even loss of effect. Notably, mesalamine, azathioprine, methotrexate, and biologic medications can all be affected by concomitant alcohol intake via a variety of mechanisms.

Urinary Symptoms and Bladder Voiding Dysfunction Are Common in Young Men with Defecatory Disorders: A Retrospective Evaluation.

BACKGROUND AND AIMS: Lower urinary tract symptoms (LUTS) are frequently reported by constipated patients. Prospective studies investigating the association between defecatory disorders (DDs) and voiding dysfunction, predominantly in women, have reported conflicting results. This study investigated (1) the prevalence of LUTS in young men with DDs and (2) the association between objectively documented DDs and voiding dysfunction in constipated young men with LUTS. METHODS: We reviewed the medical records, including validated questionnaires, of men aged 18-40 with confirmed DDs treated with pelvic floor physical therapy (PT) at our institution from May 2018 to November 2020. In a separate group of constipated young men with LUTS who underwent high-resolution anorectal manometry (HRM), rectal balloon expulsion test (BET), and uroflowmetry, we explored the relationship between DDs and voiding dysfunction. RESULTS: A total of 72 men were evaluated in the study. Among 43 men receiving PT for a proven DD, 82% reported ≥ 1 LUTS, most commonly frequent urination. Over half of these men experienced a reduction in LUTS severity after bowel-directed pelvic floor PT. Among 29 constipated men with LUTS who had undergone HRM/BET and uroflowmetry, 28% had concurrent defecatory and voiding dysfunction, 10% had DD alone, 14% had only voiding dysfunction, and 48% had neither. The presence of DD was associated with significantly increased odds of concurrent voiding dysfunction (odds ratio 9.3 [95% CI 1.7-52.7]). CONCLUSIONS: Most young men with DDs experience LUTS, which may respond to bowel-directed physical therapy. Patients with DD and urinary symptoms have increased odds of voiding dysfunction.

Is exposure to family member incarceration during childhood linked to diabetes in adulthood? Findings from a representative community sample.

OBJECTIVES: Diabetes is a prevalent and serious public health problem, particularly among older adults. A robust literature has shown that adverse childhood experiences contribute to the development of health problems in later life, including diabetes. Family member incarceration during childhood is an under-investigated yet increasingly common adverse childhood experience in the United States. The purpose of this study was to investigate the relationship between family member incarceration during childhood and diabetes in adulthood, while considering the role of gender as well as the impact of a range of potential confounds. METHODS: A large representative community sample of adults aged 40 and older (n = 8790 men, 14,255 women) was drawn from the Behavioral Risk Factor Surveillance System 2012 optional adverse childhood experiences module to investigate the association between family member incarceration during childhood and diabetes. For each gender, nine logistic regression analyses were conducted using distinct clusters of variables (e.g. socioeconomic status and health behaviors). RESULTS: Among males, the odds of diabetes among those exposed to family member incarceration during childhood ranged from 2.00 to 1.59. In the fully adjusted model, they had elevated odds of 1.64 (95% confidence interval = 1.27, 2.11). Among women, the odds of diabetes was much lower, hovering around 1.00. CONCLUSION: Findings suggest that family member incarceration during childhood is associated with diabetes in men, even after adjusting for a wide range of potential risk factors (e.g. sociodemographics, health behaviors, healthcare access, and childhood risk factors). Future research should explore the mechanisms linking family member incarceration during childhood and long-term negative health outcomes in men.

Clinically differentiating life-course-persistent and adolescence-limited conduct problems: Is age-of-onset really enough?

One important subtyping of behavior problems is Moffitt's (1993) "life-course-persistent" (LCP) and "adolescent limited" (AL) categories of antisocial behavior, which she differentiated in terms of high impulsivity, poor academic performance, and aggression. These problems may be exacerbated by the cumulative effects of chronic stress. Copious evidence has documented validity and developmental differences between these subtypes, whereas far fewer data exist regarding their clinical utility, in spite of the Diagnostic and Statistical Manual's nomenclature including corresponding subtypes based on age-of-onset of behavioral symptoms. The present study evaluated how well age-of-onset based subtyping identifies distinct developmental patterns of antisocial behavior corresponding to Moffitt's subtypes in terms of risk factors and gender between LCP and AL in a prospective sample of chronically stressed youth. A computerized assessment tool (ALEXSA©) was used to obtain data from 1,147 youth aged 8-16. Implications for clinical assessment and intervention strategy, particularly with stressed youth, are discussed.

Primary Versus Secondary Diagnosis of Generalized Anxiety Disorder in Youth: Is the Distinction an Important One?

Examine whether children with a primary diagnosis of generalized anxiety disorder (GAD) differ from children with a secondary diagnosis of GAD on clinician, parent, teacher, and youth-report measures. Based on consensus diagnoses, 64 youth referred to a general outpatient assessment clinic were categorized as having either a primary or secondary diagnosis of GAD. A semi-structured diagnostic interview was used to guide diagnostic decisions and assign primary versus secondary diagnostic status. We predicted that youth with a primary GAD diagnosis would present with greater anxiety symptomatology and symptom impairment on a variety of anxiety-related measures than youth with a secondary GAD diagnosis. Contrary to our hypotheses, no differences were found between those with primary versus secondary GAD diagnoses on measures of symptom severity and clinical impairment, comorbid diagnoses, or youth and teacher-report measures. Our findings have potential implications for the current practice of requiring primary anxiety diagnostic status as an inclusion criterion in clinical research and treatment outcome studies. Assuming our findings are confirmed in larger samples and with other anxiety disorders, future clinical trials and basic psychopathology research might not exclude youth based on absence of a particular anxiety disorder as the primary disorder but rather include individuals for whom that anxiety disorder is secondary as well.

Attentional control mediates fearful responding to an ecologically valid stressor.

BACKGROUND AND OBJECTIVES: Attentional control (AC) is defined as the ability to voluntarily shift and disengage attention and is thought to moderate the relationship between preexisting risk factors for fear and the actual experience of fear. DESIGN: This longitudinal study elaborates on current models of AC by examining whether AC moderates or mediates effects of an ecologically valid stressor (a college examination) and also whether AC is predictive of state-like fear over longer timescales than previously reported. METHODS: Based on previous findings, we hypothesized that AC would moderate the relationship between trait anxiety and affective distress in response to the examination stressor. We also tested a competing mediational model based on AC theory. These models were tested in two separate samples (sample 1, N = 219; sample 2, N = 129; Total N = 348) at two time points, at the beginning of a college semester in a large undergraduate class and 5 minutes prior to a college examination. RESULTS: Mediation but not moderation of anxiety by AC was supported in both samples using multiple dependent measures. CONCLUSIONS: We conclude that AC may be useful in predicting affective distress in naturalistic settings, particularly in cases where anxiety is anticipatory.

Social anxiety predicts aggression in children with ASD: clinical comparisons with socially anxious and oppositional youth.

The present study examined the degree to which social anxiety predicts aggression in children with high functioning autism spectrum disorders (HFASD, n = 20) compared to children with Social Anxiety Disorder (SAD, n = 20) or with Oppositional Defiant Disorder or Conduct Disorder (ODD/CD, n = 20). As predicted, children with HFASD reported levels of humiliation/rejection fears commensurate with children with SAD and exhibited aggression at levels commensurate with ODD/CD, and a curvilinear relationship between social fears and aggression was found in the HFASD group only. Results indicate the possibility of an optimal level of social-evaluative fears that is unique for children with HFASD; too little social fear or too much may contribute to problems with aggression.

Biased self-perceptions, peer rejection, and aggression in children.

This study examined whether children's biased self-perceptions of peer acceptance are associated in a linear or curvilinear fashion with aggression, whether associations are moderated by peer rejection status, and whether associations apply uniquely to reactive aggression. Children in the 4th through 7th grades completed a self-report measure on their social functioning (SPPC; Harter 1982), and teachers reported on children's social functioning and aggression. Self-perceptual bias was operationalized as the standardized residual difference between children's self-perceptions and their teachers' perceptions of their peer acceptance. Rejected status moderated associations between biased self-perceptions and reactive aggression. Among non-rejected children, biased perceptions were not significantly associated with reactive aggression. In contrast, among peer-rejected children, reactive aggression was elevated in those who greatly underestimated as well as in those who even modestly overestimated their peer acceptance. This pattern was observed whether or not proactive aggression was statistically controlled. In contrast, biased self-perceptions were not associated with proactive aggression for rejected or nonrejected children. Implications are discussed with regard to future research and potential interventions for aggressive children.

Ethnic and sex differences in children's depressive symptoms: mediating effects of perceived and actual competence.

Examined ethnic and sex differences in depressive symptoms, along with hypothesized mediators of those differences (academic achievement, peer acceptance), for a sample of African American (n = 272) and Euro-American (n = 630) children in Grades 3 to 5. Group comparisons revealed a significant Ethnicity x Sex interaction in depressive symptoms. African American boys reported more depressive symptoms than Euro-American boys, whereas African American and Euro-American girls reported comparable levels of depressive symptoms. Sex differences in depressive symptoms differed by ethnicity: Boys were more depressed than girls in the African American group whereas girls were more depressed than boys in the Euro-American group. The Ethnicity x Sex interaction was mediated by academic achievement, but not peer acceptance. These findings have implications for understanding the mechanisms underlying depressive symptoms in preadolescence and for developing interventions to prevent depression.