Current Role of Monoclonal Antibody Therapy in Pediatric IBD: A Special Focus on Therapeutic Drug Monitoring and Treat-to-Target Strategies.

In the last two decades, biologicals have become essential in treating children and adolescents with inflammatory bowel disease. TNF-α inhibitors (infliximab, adalimumab and golimumab) are preferentially used. Recent studies suggest that early application of TNF-α inhibitors is beneficial to inducing disease remission and preventing complications such as development of penetrating ulcers and fistulas. However, treatment failure occurs in about one third of pediatric patients. Particularly, children and adolescents differ in drug clearance, emphasizing the importance of pharmacokinetic drug monitoring in the pediatric setting. Here, current data on the choice and effectiveness of biologicals and therapeutic drug monitoring strategies are reviewed.

Significant advantages for first line treatment with TNF-alpha inhibitors in pediatric patients with inflammatory bowel disease - Data from the multicenter CEDATA-GPGE registry study.

Background and aims: In recent years, biological agents, such as anti-TNF-α blockers, have been introduced and have shown efficacy in pediatric patients with inflammatory bowel disease (IBD). Here, the prescription mode differentiated into a first/second line application, and efficacy and side effects are evaluated beginning from 2004 until today. Methods: Statistical analyses of the prospective and ongoing CEDATA multicenter registry data from the Society of Pediatric Gastroenterology and Nutrition (GPGE) were performed for patients receiving a biological agent at least once during the period from June 2004 until November 2020 (n = 487). The analyzed parameters were patient demographics, disease extent and behavior, prior or concurrent therapies, duration and outcome of biological therapy, disease-associated complications, drug-related complications, laboratory parameters and treatment response as determined by the Physician's Global Assessment. Results: Crohn's disease (CD) was present in 71.5% of patients, and 52% were boys. Patients showed high disease activity when receiving a first-line TNF-α blocker. After 2016, patients who failed to respond to anti-TNF-α induction therapy were treated with off-label biologics (vedolizumab 4.3% and ustekinumab 2.1%). Propensity score matching indicated that patients with CD and higher disease activity benefitted significantly more from early anti-TNF-α therapy. This assessment was based on a clinical evaluation and lab parameters related to inflammation compared to delayed second-line treatment. Additionally, first-line treatment resulted in less treatment failure and fewer extraintestinal manifestations during TNF-α blockade. Conclusion: First-line treatment with anti-TNF-α drugs is effective and safe. An earlier start significantly reduces the risk of treatment failure and is associated with fewer extraintestinal manifestations during longitudinal follow-up.

Sleep better, feel better? Effects of a CBT-I and HT-I sleep training on mental health, quality of life and stress coping in university students: a randomized pilot controlled trial.

BACKGROUND: The SWIS sleep training for university students showed promising results regarding subjective and objective sleep parameters. As sleep disorders and impaired sleep quality are closely related to various aspects of mental health, the current study examines the effects of the SWIS sleep training on mental health in university students. METHODS: Fifty six university students (M = 25.84, SD = 5.06) participated in the study, 68% were women. Forty one were randomly assigned to the SWIS treatment (pre-post-follow-up), 15 to a Waiting List Control condition (WLC, pre-post). Besides sleep-related measures, the students completed four online questionnaires measuring mental health, quality of life and stress coping strategies. Effect sizes for the pre-post data were compared between the conditions, long-term effects were calculated with repeated measures ANOVA or Friedman ANOVA. Long-term clinical changes were analyzed with the Reliable Change Index (RCI). RESULTS: The pre-post comparisons between SWIS and WLC revealed lower depression scores in both conditions, a better physical state in the SWIS condition and less maladaptive stress coping strategies in the WLC students. The long-term results of SWIS provided significant improvements regarding the students' somatic complaints, reduced anxiety, an improved physical state and a better quality of life with moderate to large effect sizes. Most of the significant improvements occurred between pre- and follow-up measurement. These statistically significant results were also reflected in clinically significant changes from pre- to follow-up-test. CONCLUSIONS: SWIS and WLC condition both improved in two mental health variables immediately after the training. These findings may be explained by unspecific treatment expectation effects in the WLC. Interestingly, most mental health outcomes showed significant improvements after 3 months, but not immediately after the training. These positive long-term effects of the SWIS training on mental health indicate that the transfer of strategies might simply need more time to affect the students' mental health. TRIAL REGISTRATION: The current study was retrospectively registered at German Clinical Trials Register (ID: DRKS00014338 , registration date: 20.04.2018, enrolment of first participant: 14.04.2015).

Sleep problems in university students - an intervention.

INTRODUCTION: Up to 60% of all college students suffer from a poor sleep quality, and 7.7% meet all criteria of an insomnia disorder. Sleep problems have a great impact on the students' daily life, for example, the grade point average. Due to irregular daytime routines, chronotype changes, side jobs and exam periods, they need specialized treatments for improving sleep. "Studieren wie im Schlaf" (SWIS; (studying in your sleep)) is a multicomponent sleep training that combines Cognitive Behavioral Therapy for Insomnia and Hypnotherapy for Insomnia to improve students' sleep, insomnia symptoms and nightmares. The aim of the present study is to evaluate the acceptance, feasibility and the first effects of SWIS. METHODS: Twenty-seven students (mean =24.24, standard deviation =3.57) participated in a study of pre-post design. The acceptance and feasibility were measured with questionnaires. In addition, the Pittsburgh Sleep Quality Index (PSQI), sleep logs and actigraphy were implemented. Further variables encompassed daytime sleepiness, sleep-related personality traits and cognitions about sleep. RESULTS: Seventy-four percent of the participants reported symptoms of an insomnia disorder, and 51.9% fulfilled all criteria of an insomnia disorder according to the Diagnostic and Statistical Manual of Mental Disorders (fifth edition). Correspondingly, the students suffered from clinically relevant sleep problems according to the PSQI. The SWIS sleep training is a well-accepted and feasible program. Significant improvements were observed in the subjective sleep quality and sleep-related personality traits, as well as clinical improvements in objective sleep measures. DISCUSSION: Findings showed that SWIS is a feasible program for the treatment of sleep problems in college and university students due to its various effects on sleep and cognitive outcomes. Further evaluation of follow-up measurements and additional variables, that is, cognitive performance and mental health, is needed.

Sleep and somatic complaints in university students.

BACKGROUND: Sleep problems are common among university students. Poor sleep is associated with impaired daily functioning, increased risk of psychiatric symptoms, and somatic complaints such as pain. Previous results suggest that poor sleep exacerbates pain, which in turn negatively affects sleep. The purpose of the present study was to determine prevalence rates, comorbidity, and role of depression as a factor of moderating the relationship between sleep and physical complaints in German university students. SAMPLES AND METHODS: In total, 2443 German university students (65% women) completed a web survey. Self-report measures included the Pittsburg Sleep Quality Index, three modules of the Patient Health Questionnaire, and a questionnaire on the functional somatic syndromes (FSSs). RESULTS: More than one-third (36.9%) reported poor sleep as assessed by the Pittsburgh Sleep Quality Index. Somatoform syndrome was identified in 23.5%, and the prevalence of any FSS was 12.8%. Self-reported sleep quality, sleep onset latency, sleep disturbances, use of sleep medications, and daytime dysfunctioning were significant predictors of somatoform syndrome, whereas sleep efficiency and sleep duration influenced somatic complaints indirectly. Moderate correlations were found between stress, anxiety, somatoform syndrome, depression, and overall sleep quality. The effect of somatic complaints on sleep quality was associated with the severity of depression. Anxiety shows direct effects on somatization and depression but only indirect associations with sleep quality.

Sleep disturbances and mental strain in university students: results from an online survey in Luxembourg and Germany.

OBJECTIVES: This study examined the prevalence of sleep disturbances and mental strain in students from two European countries, Luxembourg and Germany. METHODS: A total of 2831 students took part in an online survey, with 2777 students from Germany and 184 students from Luxembourg. Sleep disturbances were assessed with the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale, and aspects of mental strain using the Patient Health Questionnaire, the Social-Interactive-Anxiety Scale, the self-efficacy questionnaire and the test anxiety questionnaire. In addition, we also assessed students' chronotypes. RESULTS: Across the whole sample mean scores on the sleep questionnaires were above the cut-off for clinically relevant sleep problems, indicating an increased prevalence of sleep disturbances in students from both countries. Sleep quality was impaired in 42.8%, and 17.9% showed clinically relevant scores. Overall 25.5% reported elevated depression and 13.3% social phobia symptoms, while 45% indicated elevated stress levels. Sleep quality, daytime sleepiness, chronotype, depression scores, stress levels, test anxiety, and self-efficacy differed significantly between men and women, but there were no differences between countries. CONCLUSIONS: Sleep disturbances and mental strain in students are common, with the current results replicating previous findings. Students from Luxembourg and Germany are affected equally.