Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease

AbstractBackground & Aims: Interleukin (IL)-10 is a cytokine with potent anti-inflammatory properties. We investigated the safety and efficacy of different doses of human recombinant (rhu)IL-10 in patients with Crohn's disease (CD). Methods: A prospective, multicenter, double-blind, placebo-controlled study was conducted in 329 therapy-refractory patients with CD. Clinical improvement was defined by a reduction of the Crohn's Disease Activity Index (CDAI) by 100 points or more and clinical remission by a decrease of the CDAI to Results: Subcutaneous treatment with rhuIL-10 over 28 days induced a fully reversible, dose-dependent decrease in hemoglobin and thrombocyte counts but no clinically significant side effects. No differences in the induction of remission were observed between rhuIL-10 groups (1 μg, 18% [9.6–29.2]; 4 μg, 20% [11.3–32.2]; 8 μg, 20% [11.1–31.8]; 20 μg, 28% [18–40.7]; and placebo, 18% [9.6–29.6]). Clinical improvement was observed in 46% (33.7–59) in the 8-μg/kg rhuIL-10 group in comparison with 27% (17–39.6) in patients taking placebo. Responders to rhuIL-10 showed inhibition of NF-κB p65 activation in contrast to nonresponders. Conclusions: Up to 8 μg/kg of rhuIL-10 was well tolerated. A tendency toward clinical improvement but not remission was observed in the 8-μg/kg dose group. Further studies should delineate which subgroups of patients with CD benefit from rhuIL-10 therapy.GASTROENTEROLOGY 2000;119:1461-147

Posttraumatic Stress, Alcohol Use, and Alcohol Use Motives Among Firefighters: The Mediating Role of Anxiety Sensitivity

Firefighters are frequently exposed to high-risk, potentially life-threatening events, and as a result, they are vulnerable to developing posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD). The current study aimed to examine the mediating role of anxiety sensitivity (AS; fear of anxiety-related sensations) in the association of PTSD symptomology with alcohol use and alcohol use motives among a large sample of firefighters. It was hypothesized that heightened PTSD symptom severity would be indirectly associated with alcohol use and alcohol use coping motives, specifically, through high AS. This study is a secondary analysis of data from a larger study examining stress and health behaviors among firefighters. Participants were comprised of 652 urban firefighters who endorsed DSM-5 PTSD Criterion A trauma exposure and lifetime alcohol use. Firefighters completed an online questionnaire battery. Descriptive statistics and bivariate correlations were calculated for all study variables. A series of path analyses were conducted and regression coefficients for each hypothesized path were evaluated. Covariates included number of years in the fire service and trauma load (i.e., number of traumatic event types experienced). After accounting for covariates, AS partially mediated the association between PTSD symptom severity and alcohol use coping motives (indirect effect = .054, 95% CI [.006, .110]), conformity motives (indirect effect = .095, 95% CI [.034, .161]), and social motives (indirect effect = .054, 95% CI [.008, .109]). However, AS did not significantly mediate the relationship between PTSD symptom severity and enhancement motives (indirect effect = .047, 95% CI [-.002, .105]) or alcohol use severity (indirect effect = .026, 95% CI [-.026, .082]). Results indicate that AS reduction techniques may be effective in PTSD/AUD interventions for firefighters. Clinical and research implications are discussed.Psychology, Department o

The Role of Anxiety Sensitivity in the Relationship Between Childhood Maltreatment and Sleep Disturbance

Introduction: Individuals who have experienced childhood maltreatment are vulnerable to developing various mental disorders, such as PTSD, and are more likely to experience sleep disturbance, which furthers their risk of developing comorbid disorders. Anxiety sensitivity (AS) is a transdiagnostic mechanism with clinical relevance to both PTSD and sleep disturbance. The current study examined the role of AS in the association between childhood maltreatment and sleep disturbance among a sample of psychiatric inpatients. Childhood maltreatment severity was expected to be associated with elevated AS, which in turn, was expected to be positively associated with sleep disturbance. Childhood maltreatment was hypothesized to be indirectly associated with sleep disturbance through AS. Exploratory analyses were conducted to further elucidate this association by examining the effects of specific types of childhood maltreatment. Covariates included gender and a positive substance use urinalysis screening at intake. Methods: Participants included 88 psychiatric inpatients (62.5% male; Mage= 33.32, SD= 11.07) who reported experiencing childhood maltreatment via an online questionnaire battery. Results: AS was positively associated with both childhood maltreatment severity and sleep disturbance. Childhood maltreatment severity was indirectly associated with sleep disturbance, through AS. Exploratory analyses revealed that the main analysis findings did not differ based on childhood maltreatment type. Conclusions: Given the malleability of AS via brief AS-focused interventions, these findings have the potential to inform care and improve clinical outcomes among psychiatric inpatient populations.Psychology, Department ofHonors Colleg