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Osteoarthritis (OA) is a chronic and degenerative joint disease affecting more than 500 million patients worldwide with no disease-modifying treatment approved to date. Several publications report on the transforming growth factor β-activated kinase 1 (TAK1) as a potential molecular target for OA, with complementary anti-catabolic and anti-inflammatory effects. We report herein on the development of TAK1 inhibitors with physicochemical properties suitable for intra-articular injection, with the aim to achieve high drug concentration at the affected joint, while avoiding severe toxicity associated with systemic inhibition. More specifically, reducing solubility by increasing crystallinity, while maintaining moderate lipophilicity proved to be a good compromise to ensure high and sustained free drug exposures in the joint. Furthermore, structure-based design allowed for an improvement of selectivity versus interleukin-1 receptor-associated kinases 1 and 4 (IRAK1/4). Finally, TAK-756 was discovered as a potent TAK1 inhibitor with good selectivity versus IRAK1/4 as well as excellent intra-articular pharmacokinetic properties.

Objective: This retrospective multicenter study aimed to evaluate surgical versus conservative treatment in patients with hypopharyngeal and laryngeal cancer under real world conditions., Methods: This study included 2307 patients diagnosed with hypopharyngeal or laryngeal squamous cell carcinoma (SCC) in five German tertiary head and neck centers between 01/2004 and 12/2014. Overall, 783 patients with advanced SCC consecutively underwent laryng(opharyng)ectomy (L(P)E). Patient chart data regarding age, sex, tumor location, TNM status, grading, indication for L(P)E, treatment modalities, R status, postoperative complications, and hospitalization time were analyzed. Patients with lacking data and incomplete staging and those who refused treatment or did not comply with the recommended treatment were excluded from survival analysis., Results: A slight but significant increase was observed in L(P)E, referring to an increasing rate of tumor recurrence. While T1/2N0M0 laryngeal and hypopharyngeal cancer patients showed comparable overall survival (OS) for surgical and conservative treatment, surgery showed significantly better OS in lymph node-positive individuals and locally advanced tumor stages. Tumor recurrence occurred in more than one-third of the cases. In particular, in early glottic cancer recurrence, L(P)E represents a curative and safe treatment option, whereas in supraglottic and hypopharyngeal cancer, L(P)E was associated with reduced survival rates. Notably, 36% of patients with supraglottic cancer and 59% of patients with hypopharyngeal cancer recurrence could only be treated with palliative care., Conclusion: Comparable survival rates were demonstrated for cT1/2N0M0 laryngeal and hypopharyngeal SCC compared with primary chemo-/radiotherapy and larynx-preserving surgery. Better OS was achieved after surgery in nodal-positive patients and in those with locally advanced disease. Tumor recurrence should be anticipated in up to 39% of cases. Glottic cancer recurrence can be successfully and safely treated with L(P)E, whereas OS is reduced in hypopharyngeal cancer and possibly in supraglottic cancer., (© 2024. The Author(s).)

Background: Mental disorders during pregnancy and the postpartum period can have far-reaching consequences. To enhance peripartum mental well-being and prevent peripartum mental disorders, internet- and mobile-based interventions appear promising. They can overcome help-seeking barriers associated with face-to-face conditions and have proven to be effective. However, previous findings are scarce and mixed. The primary objectives of this study were to assess the feasibility and acceptability of an internet-based program aimed at enhancing peripartum mental well-being and preventing postpartum depression., Methods: In total, 149 pregnant, German-speaking women were assigned to the internet-based intervention PandaMom. The program comprises a total of 10 basic and supplementary modules related to pregnancy and postpartum, based on cognitive-behavioral principles. Additionally, PandaMom offers professional, individualized guidance and a moderated group-chat. Assessments were conducted at baseline (pre-intervention), as well as two and five weeks postpartum. The primary outcomes included feasibility, user satisfaction, and adherence to the intervention. Secondary outcomes included depressive symptomatology, anxiety and stress., Results: PandaMom was found to be feasible, and evaluation of module content and length satisfaction indicated that the intervention was well accepted. Nearly half of the participants utilized the guidance service by responding to individual messages from their intervention moderator. Regarding working alliance, participants reported a strong bond with their intervention moderator. Of the 149 participants, 132 logged into the platform at least once. 113 participants accessed at least one module, with an average of 4.7 modules opened per participant. However, only 16 participants completed the basic modules., Conclusion: The findings of this study support previous evidence that internet-and mobile-based interventions are feasible and acceptable during pregnancy and the postpartum period. Further research is needed to address the challenge of low adherence and to evaluate the efficacy of PandaMom., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

This Virtual Issue of the International Journal of Eating Disorders honors the legacy of the late Dr. C. Barr Taylor in the eating disorders (EDs) field. For decades, Dr. Taylor led the way in not only conducting the research needed to achieve the ultimate goal of making affordable, accessible, and evidence-based care for EDs available to all, but also nurturing the next generation of scientific leaders and innovators. Articles included in this Virtual Issue are a selection of Dr. Taylor's published works in the Journal in the past decade, spanning original research, ideas worth researching, commentaries, and a systematic review. We hope this Virtual Issue will inspire the next generation of research in EDs, and equally, if not more importantly, the next generation of young investigators in the field. We urge the field to continue and build upon Dr. Taylor's vision-to increase access to targeted prevention and intervention for EDs in innovative and forward-thinking ways-while embracing his unique and powerful mentorship style to lift up early career investigators and create a community of leaders to address and solve our field's biggest challenges., (© 2024 Wiley Periodicals LLC.)

Background: Although effective treatments for bulimic-spectrum eating disorders exist, access is often delayed because of limited therapist availability and lengthy waiting lists. Web-based self-help interventions have the potential to bridge waiting times for face-to-face treatment and overcome existing treatment gaps., Aims: This study aims to assess the effectiveness of a web-based guided self-help intervention (everyBody Plus) for patients with bulimia nervosa, binge eating disorder and other specified feeding and eating disorders who are waiting for out-patient treatment., Method: A randomised controlled trial was conducted in Germany and the UK. A total of 343 patients were randomly assigned to the intervention 'everyBody Plus' or a waitlist control condition. The primary outcome was the number of weeks after randomisation until a patient achieved a clinically relevant improvement in core symptoms for the first time. Secondary outcomes included eating disorder attitudes and behaviours, and general psychopathology., Results: At 6- and 12-month follow-up, the probability of being abstinent from core symptoms was significantly larger for the intervention group compared with the control group (hazard ratio: 1.997, 95% CI 1.09-3.65; P = 0.0249). The intervention group also showed larger improvements in eating disorder attitudes and behaviours, general psychopathology, anxiety, depression and quality of life, compared with the control group at most assessment points. Working alliance ratings with the online therapist were high., Conclusions: The self-help intervention everyBody Plus, delivered with relatively standardised online guidance, can help bridge treatment gaps for patients with bulimic-spectrum eating disorders, and achieve faster and greater reductions in core symptoms.

Introduction: The role of personality in shaping engagement with aesthetics in science has been almost entirely unexplored. Whereas artists and arts settings (e.g., museums) are well-studied from a psychological perspective, the practice of science has often been seen as purely rational or dry. In response, this study presents novel findings on the critical role of scientists' individual differences, which shape their engagement with aesthetics, such as the frequency of their experiences of beauty, wonder, and awe in their scientific work., Methods: Based on a very large and representative four-country study of scientists in the fields of biology and physics ( N  = 3,092), this study analyzed the associations of Big Five personality traits among scientists with (i) dispositional aesthetics (DPES-awe), (ii) the frequency of aesthetic experiences in scientific work, and (iii) aesthetic sensitivity in science. These survey-weighted OLS regression models included extensive statistical controls for sociodemographic factors., Results: As hypothesized, openness is positively, and neuroticism is negatively linked with dispositional aesthetics, the frequency of aesthetic experiences in scientific work, and aesthetic sensitivity in science. Unexpectedly, agreeableness and conscientiousness (but not extraversion) are highly significant and strong predictors of the three trait and state aesthetic engagement variables., Discussion: The aesthetic engagement and personality framework of this paper is empirically supported and demonstrates the importance of personality types of scientists in the practice of science. The unexpectedly strong association of agreeableness with aesthetic engagement points to the importance of cooperation, collaboration, and communication to maximize scientific creativity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jacobi, Varga, Jessani and Vaidyanathan.)

Introduction: Limited research exists on intervention efficacy for comorbid subclinical anxiety and depressive disorders, despite their common co-occurrence. Internet- and mobile-based interventions (IMIs) are promising to reach individuals facing subclinical symptoms., Objective: This study aimed to evaluate the efficacy of a transdiagnostic and self-tailored IMI in reducing subclinical anxiety and depressive symptom severity with either individualized (IG-IMI) or automated (AG-IMI) guidance compared to a waitlist control group with care-as-usual access (WLC)., Methods: Participants included 566 adults with subclinical anxiety (GAD-7 ≥ 5) and/or depressive (CES-D ≥16) symptoms, who did not meet criteria for a full-syndrome depressive or anxiety disorder. In a three-arm randomized clinical trial, participants were randomized to a cognitive behavioral 7-session IMI plus booster session with IG-IMI (n = 186) or AG-IMI (n = 189) or WLC (n = 191). Primary outcomes included observer-rated anxiety (HAM-A) and depressive (QIDS) symptom severity 8 weeks after randomization assessed by blinded raters via telephone. Follow-up outcomes at 6 and 12 months are reported., Results: Symptom severity was significantly lower with small to medium effects in IG-IMI (anxiety: d = 0.45, depression: d = 0.43) and AG-IMI (anxiety: d = 0.31, depression: d = 0.32) compared to WLC. No significant differences emerged between guidance formats in primary outcomes. There was a significant effect in HAM-A after 6 months favoring AG-IMI. On average, participants completed 85.38% of IG-IMI and 77.38% of AG-IMI., Conclusions: A transdiagnostic, self-tailored IMI can reduce subclinical anxiety and depressive symptom severity, but 12-month long-term effects were absent. Automated guidance holds promise for enhancing the scalability of IMIs in broad prevention initiatives., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: The 2020 Law on Access to the Voluntary Interruption of Pregnancy is a landmark piece of legislation regarding access to abortion in Argentina. Under the new law, abortion is legal up to 14 weeks and 6 days gestation, with exceptions made to the gestational age limit to save a woman´s life, to preserve a woman´s health, and in case of rape. However, widespread refusal to provide care by authorized health providers (due to conscientious objection or lack of awareness of the new law) could hinder access to legal abortion. This study aimed to assess knowledge of the current legal framework and willingness to perform abortions by authorized professionals in Argentina, to compare perceptions about any requirements necessary to perform abortions on legal grounds between willing and unwilling providers and to explore factors associated with refusal to provide care., Methods: We conducted a cross-sectional study based on a self-administered, anonymous survey to authorized abortion providers in public health facilities in four provinces of Argentina., Findings: Most authorized providers knew the grounds upon which it is currently legal to perform abortions; however, almost half reported being unwilling to perform abortions, mainly due to conscientious objection. Both willing and unwilling providers believed there were additional requirements not actually stipulated by law. Using logistic regression, we found that province where providers serve, working in a tertiary level facility, and older age were factors associated with unwillingness to provide care., Conclusions: The results of our study indicate that, even in a favorable legal context, barriers at the provider level may hinder access to abortion in Argentina. They help to demonstrate the need for specific actions that can improve access such as training, further research and public policies that guarantee facilities have sufficient professionals willing to provide abortion care., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Vázquez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective/background: Despite its high prevalence, little information is available about the course of insomnia symptoms over the life span. In this study, we analyzed the self-reported insomnia symptoms of the general population over more than 20 years, covering young up to middle adulthood., Patients/methods: Data from waves 12 to 32 of the Saxon Longitudinal Study (1996-2021), were analyzed. Based on data from the 12th wave, n = 115 adults (48 men (41.7%), 67 women (58.3%), M age  = 23.59, SD = 0.59) completed the G-Score Item #3 in the following 18 waves, thus forming the basis for our analyses. The G-Score Item #3 reads "In the last 12 months, have you had the following complaints? Please indicate how often they occurred - Insomnia". The G-Score Item #3 was dichotomized using a cut-off score of 2, and prevalence and incidence rates were calculated by gender., Results: The minimum prevalence rate was 23.48% (M age  = 32.11, SD = 0.40), and the maximum was 47.83% (M age  = 48.43, SD = 0.64), indicating an increase in insomnia symptoms with age. In most cases, no evidence was found for gender differences in prevalence rates. The incidence rates were 10.43% for the 1st year of follow-up and 8.7% for the 5th year and 6th year of follow-up, respectively., Conclusions: This study provides further evidence for the high prevalence rates of insomnia symptoms in the general population. As this study is the first epidemiological study of insomnia symptoms based on a single-item (screening) instrument, it should be rather seen as an extension than a replication of previous study findings., Competing Interests: Declaration of competing interest Franziska Klimt, Clara Jacobi, Elmar Brähler, Yve Stöbel-Richter, Markus Zenger and Hendrik Berth declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Peripartum mental disorders are highly prevalent conditions and associated with adverse outcomes for the mother, the infant and the whole family. Despite the high burden, help-seeking is low. E-mental health interventions could overcome help-seeking barriers and thus improve perinatal mental health. However, usage and adherence are rather low. This study aims to assess attitudes and needs of different stakeholder groups and to identify relevant topics to develop an intervention meeting the needs of pregnant and postpartum women and thus, increasing utilization and adherence. Therefore, semi-structured interviews and focus groups with pregnant women (n = 3), mothers (n = 4), women who have suffered from a postpartum mood disorder in the past (n = 5), gynaecologists (n = 5), and midwives (n = 5) were conducted. All interviews were audio-recorded, transcribed verbatim, and analyzed using a thematic analysis. Almost half of the stakeholders reported previous experiences with e-mental health services. Anonymity, flexibility, promoting help-seeking, or bridging waiting-time for treatment as usual were regarded as the main benefits. Concerns regarding the usefulness of e-mental health interventions, absence of face-to-face contact or lack of integration into routine care were considered as barriers. With regard to the desired program content, six main topics were identified: pregnancy and puerperium, peripartum mood swings and disorders, support options, self-care, partnership, and fatherhood. Regarding preferred characteristics of e-mental health programs, stakeholders mentioned customizability, individual guidance, evaluation of user-feedback and continuous adoption, as well as a responsive and user-friendly design. Overall, online interventions for perinatal mental health were mainly considered as beneficial. Stakeholders underlined the high need for education regarding the use and effectiveness of e-mental health, to overcome concerns and obstacles and improve acceptability. Furthermore, developing customizable and individually-guided interventions were considered as promising to increase utilization of and adherence to e-mental health interventions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Schmidt-Hantke, Jacobi. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The Student Bodies-Eating Disorders intervention (SB-ED), a digital cognitive behavior therapy-guided self-help intervention for college women with an eating disorder, is effective for reducing eating disorder psychopathology. The purpose of this study was to evaluate moderators and mediators of the SB-ED intervention. To our knowledge, this is the first evaluation of clinical mediators of a digital intervention for women with eating disorders., Method: This is an exploratory secondary analysis of a cluster randomized trial comparing the SB-ED intervention to referral to usual care among 690 women at 27 United States colleges. Moderators included body mass index (BMI), race, ethnicity, weight/shape concerns, eating disorder impairment, thin ideal internalization, depression, anxiety, and motivation for treatment, assessed at baseline. Thin ideal internalization and depressive symptoms were tested as predictors at postintervention and mediators at 2-year follow-up. Outcome was change in global eating disorder psychopathology., Results: BMI moderated the effect of the intervention at follow-up (but not posttreatment), with individuals with a lower BMI experiencing more continued improvements in eating disorder psychopathology following the intervention than individuals with a higher BMI. Thin ideal internalization mediated the effect of the intervention at follow-up, and depression partially mediated the effect of the intervention at follow-up., Conclusions: Results of the mediator analyses suggest that helping college women reduce inflated internalization of the thin ideal and improve depressive symptoms leads to improvements in eating disorder psychopathology. Results also suggest opportunities to optimize the intervention so individuals across the BMI spectrum experience ongoing improvements over time. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Lacrimal and meibomian glands contribute to the aqueous and lipid components of tear film, respectively. Their evaluation remains central to diagnosing and managing dry eye disease (DED). The review discusses the differences and reliability of various diagnostic tests and commercially available devices used for DED diagnosis. Slit-lamp-based techniques are direct palpebral lobe and tear flow assessment, Schirmer test, meibum quality and expressibility, and evaluation of tear meniscus height. Non-invasive tear meniscus height (TMH), tear break-up time (TBUT), lipid layer thickness (LLT), and meibography are machine-based diagnostic tests. The structure-function correlation of the tear-producing glands gives more comprehensive details than either information alone. Many devices are available in the market, which make DED diagnosis an easy feat, but the tests should be interpreted keeping in mind the intra-observer and inter-observer repeatability. Also, the tear film displays a huge variability as per the environmental conditions and impact of blinking. Hence, the examiner should be well versed with the techniques and repeat the test two to three times to obtain an average reading, which is more reliable. The recommended sequence of tests for diagnosing DED is a dry eye questionnaire, TMH, LLT, NIBUT (FBUT if non-invasive test is unavailable but should be performed after osmolarity), tear osmolarity, meibography, and ocular surface staining. Invasive tests such as Schirmer should be performed after the non-invasive tear film diagnostic testing., Competing Interests: None

Background: A growing body of evidence for digital interventions to improve sleep shows promising effects. The interventions investigated so far have been primarily web-based; however, app-based interventions may reach a wider audience and be more suitable for daily use., Objective: This study aims to evaluate the intervention effects, adherence, and acceptance of an unguided app-based intervention for individuals who wish to improve their sleep., Methods: In a randomized controlled trial, we evaluated the effects of an app-based short intervention (Refresh) to improve sleep compared with a waitlist condition. Refresh is an 8-week unguided intervention covering the principles of cognitive behavioral therapy for insomnia (CBT-I) and including a sleep diary. The primary outcome was sleep quality (insomnia symptoms) as self-assessed by the Regensburg Insomnia Scale (RIS). The secondary outcomes were depression (9-item Patient Health Questionnaire [PHQ-9] score) and perceived insomnia-related impairment., Results: We included 371 participants, of which 245 reported poor sleep at baseline. About 1 in 3 participants who were allocated to the intervention group never accessed the intervention. Active participants completed on average 4 out of 8 chapters. Retention rates were 67.4% (n=250) at postassessment and 57.7% (n=214) at the 6-month follow-up. At postintervention, insomnia symptoms in the intervention group had improved more than those in the waitlist group, with a small effect (d=0.26) in the whole sample and a medium effect (d=0.45) in the subgroup with poor sleep. Effects in the intervention group were maintained at follow-up. Perceived insomnia-related impairment also improved from pre- to postassessment. No significant intervention effect on depression was detected. Working alliance and acceptance were moderate to good., Conclusions: An app-based, unguided intervention is a feasible and effective option to scale-up CBT-I-based treatment, but intervention uptake and adherence need to be carefully addressed., Trial Registration: ISRCTN Registry ISRCTN53553517; https://www.isrctn.com/ISRCTN53553517., (©Bianka Vollert, Luise Müller, Corinna Jacobi, Mickey Trockel, Ina Beintner. Originally published in JMIR Mental Health (https://mental.jmir.org), 21.03.2023.)

Introduction: Relapse following acute treatment for anorexia nervosa (AN) is common. Evidence suggests cognitive-behavioral therapy (CBT) may be useful in the post-acute period, but few patients have access to trained providers. mHealth technologies have potential to increase access to high-quality care for AN, including in the post-acute period. The aim of this study is to estimate the preliminary feasibility and effectiveness of a CBT-based mobile intervention plus treatment as usual (TAU), offered with and without an accompanying social networking feature., Method: In the current pilot randomized controlled trial, women with AN who have been discharged from acute treatment in the past 2 months (N = 90) will be randomly assigned to a CBT-based mobile intervention plus treatment as usual (TAU), a CBT-based mobile intervention including social networking plus TAU, or TAU alone. We will examine feasibility, acceptability, and preliminary effectiveness of the three conditions in terms of reducing eating disorder psychopathology, reducing frequency of eating disorder behaviors, achieving weight maintenance, reducing depression and suicidal ideation, and reducing clinical impairment. We will examine rehospitalization and full recovery rates in an exploratory fashion. We will also examine whether the mobile intervention and social networking feature change the proposed targets and whether changes in targets are associated with benefit, as well as conduct exploratory analyses to identify within-mobile intervention predictors and moderators of outcome., Discussion: Ultimately, this research may lead to increased access to evidence-based treatment for individuals with AN and prevention of the extreme negative consequences that can result from this serious disorder., Public Significance: Relapse after acute treatment for anorexia nervosa is common, and few patients have access to trained providers to support them following acute care. This study will pilot a coached mobile app, including a social networking component, for this population. If ultimately successful, our approach could greatly increase access to evidence-based treatment for individuals with anorexia nervosa and ultimately prevent the extreme negative consequences that can result from this serious disorder., (© 2023 Wiley Periodicals LLC.)

Background: Patients with myasthenia gravis (MG) are potentially prone for a severe COVID-19 course, but there are limited real-world data available on the risk associated with COVID-19 for patients with MG. Here, we investigate whether current immunosuppressive therapy (IST) influences the risk of SARS-CoV-2 infection and COVID-19 severity., Methods: Data from the German myasthenia gravis registry were analyzed from May 2020 until June 2021 and included patient demographics, MG disease duration, comorbidities, current IST use, COVID-19 characteristics, and outcomes. Propensity score matching was employed to match MG patients with IST to those without, and multivariable binary logistic regression models were used to determine associations between IST with (1) symptomatic SARS-CoV-2 infection and (2) severe COVID-19 course, as measured by hospitalization or death., Results: Of 1379 patients with MG, 95 (7%) patients (mean age 58 (standard deviation [SD] 18) presented with COVID-19, of which 76 (80%) received IST at time of infection. 32 patients (34%) were hospitalized due to COVID-19; a total of 11 patients (12%) died. IST was a risk factor for hospitalization or death in the group of COVID-19-affected MG patients (odds ratio [OR] 3.04, 95% confidence interval [CI] = 1.02-9.06, p = 0.046), but current IST was not associated with a higher risk for SARS-CoV-2 infection itself., Discussion: In this national MG cohort study, current IST use was a risk factor for a severe disease course of COVID-19 but not for SARS-CoV-2 infection itself. These data support the consequent implementation of effective strategies to prevent COVID-19 in this high-risk group., Trial Registration Information: German clinical trial registry ( https://www.drks.de ), DRKS00024099, first patient enrolled: February 4th, 2019., (© 2022. The Author(s).)

Background: Depression and anxiety are common mental health conditions in college and university student populations. Offering transdiagnostic, web-based prevention programs such as ICare Prevent to those with subclinical complaints has the potential to reduce some barriers to receiving help (eg, availability of services, privacy considerations, and students' desire for autonomy). However, uptake of these interventions is often low, and accounts of recruitment challenges are needed to complement available effectiveness research in student populations., Objective: The aims of this study were to describe recruitment challenges together with effective recruitment strategies for ICare Prevent and provide basic information on the intervention's effectiveness., Methods: A 3-arm randomized controlled trial was conducted in a student sample with subclinical symptoms of depression and anxiety on the effectiveness of an individually guided (human support and feedback on exercises provided after each session, tailored to each participant) and automatically guided (computer-generated messages provided after each session, geared toward motivation) version of ICare Prevent, a web-based intervention with transdiagnostic components for the indicated prevention of depression and anxiety. The intervention was compared with care as usual. Descriptive statistics were used to outline recruitment challenges and effective web-based and offline strategies as well as students' use of the intervention. A basic analysis of intervention effects was conducted using a Bayesian linear mixed model, with Bayes factors reported as the effect size., Results: Direct recruitment through students' email addresses via the central student administration was the most effective strategy. Data from 35 participants were analyzed (individually guided: n=14, 40%; automatically guided: n=8, 23%; care as usual: n=13, 37%). Use of the intervention was low, with an average of 3 out of 7 sessions (SD 2.9) completed. The analyses did not suggest any intervention effects other than anecdotal evidence (all Bayes factors 10 ≤2.7)., Conclusions: This report adds to the existing literature on recruitment challenges specific to the student population. Testing the feasibility of recruitment measures and the greater involvement of the target population in their design, as well as shifting from direct to indirect prevention, can potentially help future studies in the field. In addition, this report demonstrates an alternative basic analytical strategy for underpowered randomized controlled trials., Trial Registration: International Clinical Trials Registry Platform NTR6562; https://tinyurl.com/4rbexzrk., International Registered Report Identifier (irrid): RR2-10.1186/s13063-018-2477-y., (©Felix Bolinski, Annet Kleiboer, Koen Neijenhuijs, Eirini Karyotaki, Reinout Wiers, Lisa de Koning, Corinna Jacobi, Anna-Carlotta Zarski, Kiona K Weisel, Pim Cuijpers, Heleen Riper. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 14.12.2022.)

Osteoarthritis (OA) is a common, debilitating, chronic disease with no disease-modifying drug approved to date. We discovered LNA043-a derivative of angiopoietin-like 3 (ANGPTL3)-as a potent chondrogenesis inducer using a phenotypic screen with human mesenchymal stem cells. We show that LNA043 promotes chondrogenesis and cartilage matrix synthesis in vitro and regenerates hyaline articular cartilage in preclinical OA and cartilage injury models in vivo. LNA043 exerts at least part of these effects through binding to the fibronectin receptor, integrin α 5 β 1 on mesenchymal stem cells and chondrocytes. In a first-in-human (phase 1), randomized, double-blinded, placebo-controlled, single ascending dose, single-center trial ( NCT02491281 ; sponsored by Novartis Pharmaceuticals), 28 patients with knee OA were injected intra-articularly with LNA043 or placebo (3:1 ratio) either 2 h, 7 d or 21 d before total knee replacement. LNA043 met its primary safety endpoint and showed short serum pharmacokinetics, cartilage penetration and a lack of immunogenicity (secondary endpoints). Post-hoc transcriptomics profiling of cartilage revealed that a single LNA043 injection reverses the OA transcriptome signature over at least 21 d, inducing the expression of hyaline cartilage matrix components and anabolic signaling pathways, while suppressing mediators of OA progression. LNA043 is a novel disease-modifying OA drug candidate that is currently in a phase 2b trial ( NCT04864392 ) in patients with knee OA., (© 2022. The Author(s).)

Dry Eye is one of the most common ocular diseases worldwide with an increasing number of patients. The pathogenesis of this disease is multifactorial and complex and the basis for diagnostic strategies and therapies. The current definition of dry eye disease as described in DEWS II includes inflammatory mechanisms at the ocular surface, a loss of homeostasis, hyperosmolarity of the tear film and neurosensory abnormalities. Subject symptom scores, a detailed patient history, certain diagnostic tools, and interdisciplinary interactions are necessary to enable an efficient, individualized and successful therapy. Important diagnostics include risk factor analysis, slit lamp examination, tear secretion tests, tearfilm stability tests, and tests for measuring the ocular surface inflammation., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: nein; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein. Erklärung zu nichtfinanziellen Interessen Mitglied DOG, BVA. Aktives Mitglied im Vorstand des Ressorts „Trockenes Auge und Oberflächenerkrankungen“ im BVA., (Thieme. All rights reserved.)

Background: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization., Methods: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization)., Results: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed)., Conclusions: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.

Objective: Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality., Methods: We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis., Results: Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74-6.54)., Conclusions: In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

The data sets and regression models presented here are related to the article "Point and interval estimation of decomposition error in discrete-time open tandem queues" [1]. The data sets are the first to analyze the approximation quality of the discrete-time decomposition approach and contain independent and dependent (explanatory) variables for the analysis of decomposition error, which were obtained using discrete-time queueing models and discrete-event simulation. Independent variables are the utilization parameters of the queues, and variability parameters of the service and arrival processes. Dependent variables are decomposition error with respect to the expected value and 95-percentile of the waiting time distribution at the downstream queue. This article presents multiple linear regression and quantile regression to explain the variance of the dependent variables for tandem queues with equal traffic intensity at both queues and for tandem queues with downstream bottlenecks, respectively., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier Inc.)

Southeast Asia harbors a young population of more than 600 million people. Socioeconomic transition within the last decades, driven by globalization and rapid economic growth, has led to significant changes in lifestyle and nutrition in many countries of this region. Hence, an increase in the number of non-communicable diseases is seen in most populations of Southeast Asia. Brunei Darussalam is the smallest country in this region, with a population of around 400,000 inhabitants. Vast hydrocarbon resources have transformed Brunei into a wealthy industrialized country within the last few decades. We compared the age distribution and prevalence of cardiovascular risk factors in ischemic stroke patients between the only stroke unit in Brunei Darussalam and a tertiary stroke center from Frankfurt/Germany. Between 2011 and 2016, a total number of 3877 ischemic stroke patients were treated in both institutions. Even after adjusting for age due to different population demographics, stroke patients in Brunei were younger compared to their German counterparts. The prevalence of hypertension and diabetes mellitus was significantly higher in young age groups in Brunei, whereas no difference was observed for older patients. The rapid socioeconomic transition might be a significant risk factor for the development of non-communicable diseases, including stroke.

Purpose: Decreased production of the aqueous component of the tear film is an important cause of the development of dry eye disease (DED). Tear production is influenced by hormones and hormone-like factors. Prolactin (PLR), a multifunctional pituitary gland hormone, is regularly present in the lacrimal gland of rats and rabbits. In humans, serum PLR concentration correlates with tear quality. To gain deeper insights of possible effects of PRL, prolactin receptor (PRLR) and prolactin inducible protein (PIP), we analyzed the three proteins in the human lacrimal apparatus and in reflex tears of healthy volunteers as well as patients suffering from DED., Methods: Gene expression of PRLR and PIP was analyzed by RT-PCR in cadaveric human lacrimal gland and ocular surface tissues, immortalized human corneal epithelial cells (HCE and hTEPI) and human Meibomian gland epithelial cells (HMGECs). At the protein level, the expression and localization of PRL, PRLR and PIP in formalin-fixed paraffin sections of the lacrimal apparatus were studied by immunohistochemistry. In addition, tear fluid from DED patients and healthy volunteers was analyzed by ELISA to determine the concentration of PRL and PIP., Results: RT-PCR analyses revealed gene expression of PRLR and PIP in human tissue samples of cornea, lacrimal glands, and eyelids, whereas only PIP, but not PRLR, was detectable in immortalized corneal epithelial cells. Immunohistochemistry revealed for the first time the expression and localization of PRL, PRLR, and PIP in human tissues of the lacrimal apparatus and at the ocular surface. PRL and PRLR were detectable in corneal epithelium, lacrimal glands, and Meibomian glands. Reflex tears from DED patients revealed significantly increased PIP concentrations, whereas PRL was undetectable in tears of DED patients and healthy volunteers., Conclusion: PRL, PRLR, and PIP are found in the lacrimal apparatus and on the ocular surface. PIP, but not PRL, is present in human tears and appears to be involved in the physiology of tear film quality. Our clinical data revealed that PIP may affect tear quality, but further functional analyses are needed to fully elucidate the effects of PRL and PIP-associated factors in tear secretion as well as in the connection of DED., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer SS declared a past co-authorship with one of the author FP to the handling editor., (Copyright © 2022 Jüngert, Paulsen, Jacobi, Horwath-Winter and Garreis.)

Background: Although preventive interventions for eating disorders in general have shown promise, interventions specifically targeting individuals at risk for anorexia nervosa (AN) are lacking., Objective: The aim of this study was to determine the efficacy of a guided, indicated web-based prevention program for women at risk for AN., Methods: We conducted a randomized controlled efficacy trial for women at risk for AN. Assessments were carried out at baseline (before the intervention), after the intervention (10 weeks after baseline), and at 6- and 12-month follow-ups (FUs). A total of 168 women with low body weight (17.5 kg/m 2 ≤BMI≤19 kg/m 2 ) and high weight concerns or with normal body weight (19 kg/m 2 2 ), high weight concerns, and high restrained eating were recruited from 3 German universities as well as on the web and randomized to Student Bodies-AN (SB-AN; intervention group [IG]) or a wait-list control group (CG). The exclusion criteria were current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-based full-syndrome eating disorders and serious medical or mental problems. The interventions were a cognitive-behavioral guided web-based prevention program (SB-AN) over 10 weeks (IG) and a wait-list CG. The primary outcomes were clinically significant changes in disordered eating attitudes and behaviors and change in BMI at 12-month FU in the group of participants who were underweight. The secondary outcomes were new onset of eating disorders, symptoms of disordered eating, and associated psychopathology., Results: Data were available for 81.5% (137/168) of the women after the intervention and for 69% (116/168) of the women at 12-month FU. At 12-month FU, the IG participants showed larger decreases in Eating Disorder Examination total scores (38/48, 79% vs 33/58, 57%) than the CG participants and the IG participants who were underweight also showed larger clinically relevant increases in BMI (15/31, 49% vs 10/32, 32%) than the CG participants, but these differences were not significant. In addition, after the intervention and at 12-month FU, we found a significant increase in continuously measured BMI for the participants who were underweight and significant improvements in disordered eating attitudes and behaviors (eg, restrained eating as well as weight and shape concerns). At all time points, the rates of new-onset eating disorder cases were (nonsignificantly) lower in the IG than in the CG and the reductions in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-based eating disorder syndromes were (nonsignificantly) higher in the IG than in the CG., Conclusions: SB-AN is the first preventive intervention shown to significantly reduce specific risk factors for, and symptoms of, AN and shows promise for reducing full-syndrome AN onset., Trial Registration: ISRCTN Registry ISRCTN70380261; https://www.isrctn.com/ISRCTN70380261., (©Corinna Jacobi, Bianka Vollert, Kristian Hütter, Paula von Bloh, Nadine Eiterich, Dennis Görlich, C Barr Taylor. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 02.06.2022.)

Purpose: NovaTears ® +Omega-3 is a water-free eye drop solution with non-animal-derived omega-3 fatty acids. It allows to supplement omega-3 fatty acids directly in the tear film of patients with dry eye disease (DED). This post-market clinical follow-up (PMCF) study evaluated for the first time the effects on clinical signs and patient symptoms of DED, and safety and tolerability of NovaTears+Omega-3 (0.2%) eye drops, when used in accordance with its approved label. Methods: A prospective, multicenter, single-arm, uncontrolled, open-label observational cohort study was performed in patients suffering from symptoms of evaporative DED. Patients were treated 4 times daily bilaterally according to the instructions for use for 8 weeks, and standard of care clinical end points were assessed at baseline and follow-up. The trial was conducted at 2 investigational sites in Germany, Europe. Results: Thirty-six patients were included and 33 completed the study. NovaTears+Omega-3 (0.2%) showed clinically and statistically significant improvements in various clinical signs, such as total corneal staining, tear film break-up time, and Meibomian gland dysfunction (MGD) score, as well as in symptoms measured by Ocular Surface Disease Index (OSDI © ) and visual analog scales over the 8-week treatment period with change from baseline P values all <0.0001. No worsening of any safety parameter (intraocular pressure, slit-lamp examination, visual acuity) was observed, and no adverse event was reported throughout the study. Conclusions: In this observational PMCF study, NovaTears+Omega-3 was safe and well tolerated. Treatment over an 8-week period resulted in significantly improved clinical signs and subjective symptoms in patients with evaporative dry eye. The study was registered at www.clinicaltrials.gov (NCT04521465).

The ocular surface is in constant interaction with the environment and with numerous pathogens. Therefore, complex mechanisms such as a stable tear film and local immune defense mechanisms are required to protect the eye. This study describes the detection, characterization, and putative role of surfactant protein G (SP-G/SFTA2) with respect to wound healing and surface activity. Bioinformatic, biochemical, and immunological methods were combined to elucidate the role of SP-G in tear film. The results show the presence of SP-G in ocular surface tissues and tear film (TF). Increased expression of SP-G was demonstrated in TF of patients with dry eye disease (DED). Addition of recombinant SP-G in combination with lipids led to an accelerated wound healing of human corneal cells as well as to a reduction of TF surface tension. Molecular modeling of TF suggest that SP-G may regulate tear film surface tension and improve its stability through specific interactions with lipids components of the tear film. In conclusion, SP-G is an ocular surface protein with putative wound healing properties that can also reduce the surface tension of the tear film.

Purpose/aim of the Study: To evaluate the improvement of ocular signs and symptoms in patients suffering from Demodex blepharitis using a combined treatment approach: use of eyelid wipes impregnated with 2.5% terpinen-4-ol (T4O) and 0.2% hyaluronic acid (HA) in the initial treatment period and investigation of maintenance of the treatment effect with the use of eyelid cleansing wipes., Materials and Methods: Fifty patients with Demodex blepharitis were treated in the initial treatment period with sterile eyelid T4O impregnated wipes for 28 days. In the following four-week maintenance period, 82% patients received sterile eyelid maintenance wipes, while 16% continued treatment with T4O impregnated wipes. Global ocular discomfort, adapted TOSS, SANDE score, and individual blepharitis symptoms were assessed by patients at day 28 and day 56. Ocular signs were evaluated by the investigator at the study visits. Investigator's assessment of the overall treatment performance, patient's assessment of treatment satisfaction, and tolerability were evaluated with questionnaires., Results: All global ocular discomfort symptoms and disease specific symptoms assessed by patients as well as all parameters evaluated by the investigators significantly improved in the initial treatment period with the application of eyelid wipes impregnated with 2.5% terpinen-4-ol until day 28. The therapeutic effect was maintained or even improved during the maintenance period under administration of mainly eyelid maintenance wipes until day 56. Both products were well tolerated. No adverse events and no clinically relevant changes in visual acuity were observed during both periods., Conclusions: Once daily treatment with T4O impregnated eyelid wipes in the initial treatment period significantly improved the ocular symptoms and signs and reduced the mite count in patients with Demodex blepharitis within four-weeks administration. Subsequent maintenance treatment with maintenance wipes for another 4 weeks preserved or further intensified the treatment success. The products were well tolerated and were convenient to use.

Background: Online preventive interventions can help to reduce the incidence of mental disorders. Whereas knowledge on stakeholders' attitudes and factors relevant for successfully integrating online treatment into existing healthcare systems is available, knowledge is scarce for online prevention., Methods: Stakeholders from Germany, Switzerland, Austria and Spain were surveyed. Potential facilitators/delivery staff (e.g. psychologists, psychotherapists) completed an online questionnaire (n = 183), policy makers (i.e. from the governing sector or health insurance providers) participated in semi-structured interviews (n = 16) and target groups/potential users of mental illness prevention (n = 49) participated in ten focus groups. Thematic analysis was used to identify their experiences with and attitudes and needs regarding online programmes to prevent mental disorders. Additionally, it was examined which groups they consider underserved and which factors they consider as fostering and hindering for reach, adoption, implementation and maintenance (cf. RE-AIM model) when integrating online prevention into existing healthcare systems., Results: Main advantages of online mental illness prevention are perceived in low structural and psychological barriers. Lack of personal contact, security, privacy and trust concerns were discussed as disadvantages. Relevant needs are high usability and target group appropriateness, evidence for effectiveness and the use of motivational tools., Conclusions: Positive attitudes among stakeholders are the key for successful integration of online mental illness prevention into existing healthcare systems. Potential facilitators/delivery staff must receive training and support to implement these programmes; the programmes must be attractive and continuously evaluated, updated and promoted to ensure ongoing reach; and existing infrastructure and contextual factors must be considered., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: Online interventions to prevent mental health problems have proven to be effective. However, knowledge about their implementation in real-world practice as well as for dissemination to the target groups in different settings is scarce. The goal of the 'ICare' network is to establish a comprehensive model of eMental-health service delivery in and across different European countries. Since implementation and dissemination are influenced by many contextual factors, in the first phase of ICare a stakeholder survey was conducted. The survey aim was to explore stakeholders' experiences, needs and attitudes regarding Internet-based prevention of mental health problems and hindering and fostering factors for implementation and dissemination. This article is part of a supplement and describes the design of the stakeholder survey. Survey results are published in separate articles in the same supplement., Methods: Based on a literature review and the individual characteristics of the ICare interventions, stakeholder groups were identified in different settings across six European countries. The RE-AIM framework guided the development of the research questions and survey instruments. A concurrent mixed methods design was applied comprising focus groups with the intended target groups of ICare interventions, an online questionnaire with potential facilitators/delivery staff and semi-structured interviews with policy makers., Conclusion: The challenge was to develop a design that allowed flexibility but at the same did not jeopardize the validity of the study. Implications drawn from this survey are not restricted to specific preventive interventions but will provide general information on how online mental illness prevention can be best implemented in various settings., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: Students beginning university are at a heightened risk for developing mental health disorders. Online prevention and early intervention programmes targeting mental health have the potential to reduce this risk, however, previous research has shown uptake to be rather poor. Understanding university stakeholders' (e.g. governing level and delivery staff [DS] and students) views and attitudes towards such online prevention programmes could help with their development, implementation and dissemination within university settings., Methods: Semi-structured interviews, focus groups and online surveys were completed with staff at a governing level, university students and DS (i.e. student health or teaching staff) from six European countries. They were asked about their experiences with, and needs and attitudes towards, online prevention programmes, as well as the factors that influence the translation of these programmes into real-world settings. Results were analyzed using thematic analysis., Results: Participating stakeholders knew little about online prevention programmes for university settings; however, they viewed them as acceptable. The main themes to emerge were the basic conditions and content of the programmes, the awareness and engagement, the resources needed, the usability and the responsibility and ongoing efforts to increase reach., Conclusions: Overall, although these stakeholders had little knowledge about online prevention programmes, they were open to the idea of introducing them. They could see the potential benefits that these programmes might bring to a university setting as a whole and the individual students and staff members., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: There is a growing body of research and evidence for the efficacy of Internet-based eating disorder (ED) prevention interventions for adults. However, much less is known about the reach, adoption, implementation and maintenance of these interventions. The RE-AIM (reach, efficacy/effectiveness, adoption, implementation, maintenance) model provides a framework to systematically assess this information., Methods: A literature search was conducted in PubMed, Web of Science and PsycINFO for articles published between 2000 and 2019. Additionally, reference lists of the studies included and existing reviews published until the end of 2020 were searched. Sixty original articles describing 54 individual studies fulfilled inclusion criteria. Data were extracted for a total of 43 RE-AIM indicators for each study. Fostering and hindering factors for reach, adoption, implementation and maintenance were assessed qualitatively., Results: Overall reporting rates were best for the RE-AIM dimensions reach (62.6%), implementation (57.0%) and effectiveness (54.2%), while adoption (24.2%) and maintenance (21.5%) had comparatively low overall reporting rates. Reporting on indicators of internal validity, such as sample size, effects or description of interventions was better than indicators relevant for dissemination and implementation in real-world settings, e.g. characteristics of non-participants, characteristics and representativeness of settings, and data to estimate cost., Conclusions: Because most Internet-based ED prevention interventions are provided in a research-funded context, little is known about their public health impact. Better reporting of factors determining external validity is needed to inform dissemination and implementation of these interventions., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: Eating disorders are causing severe consequences for those affected as well as a high burden for their carers. Although there is a substantial need for psychological assistance, different factors are hindering access to support. Internet-based interventions can help to overcome these barriers. To date, there is only little knowledge on attitudes of potential users, facilitators (e.g. psychologists) and decision makers (e.g. health insurances) regarding these interventions., Methods: We conducted focus groups with potential users (N = 30) and semi-structured interviews with potential decision makers (N = 4). Potential facilitators (N = 41) participated in an online survey. Stakeholders' experiences, attitudes, and their needs regarding Internet-based interventions for eating disorder patients and carers were assessed. Furthermore, hindering and fostering factors related to reach, adoption, implementation and maintenance were analyzed., Results: About two-thirds of the participating facilitators have heard or read about Internet-based interventions in general. In contrast, the other stakeholders mentioned to have no or little experience with such interventions. Factors like anonymity, availability and cost-effectiveness were seen as major advantages. Also disadvantages, e.g. lack of personal contact, limitations by disease severity and concerns on data safety, were mentioned. Stakeholders stated the need for interventions which are usable, evidence-based, tailored and provide personal support., Conclusion: Stakeholders considered Internet-based programmes to have more advantages than disadvantages. Effort should be put in providing systematic education to address prejudices. When offering an online intervention, stakeholders' needs, as well as a continuous evaluation and adaptation, have to be taken into account., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: The current Libyan civil war has originated many casualties, imposing medical challenges. War injuries are complex, requiring specialized knowledge and interdisciplinary assessment for adequate patient and intercultural management., Methods: This retrospective study analyzed records of 78 Libyan patients admitted from July 2016 to November 2017 to neurological and trauma surgical departments of Krankenhaus Nordwest, Frankfurt, Germany. Issues of system preparation of the hospital, demographics, injury patterns and therapies were analyzed. The chi-squared test was used to analyze differences in injury patterns in explosion and gunshot injuries., Results: Seventy-seven of seventy-eight patients were male (mean age 30.6 years). The patients received primary and secondary treatment in Tunisia (n = 39), Libya (n = 36) and Turkey (n = 23). Forty-eight patients had gunshot injuries, 37 explosion injuries, 11 both. Preparation for management of injuries included hygienic and isolation protocols, organization of interpreters and intercultural training. Patients presented with a broad variety of neurological, psychiatric and trauma surgical injuries. Fifty-six patients had sensory, 47 motor deficits. Nine reported headache, 5 vertigo, 13 visual impairment, 28 psychiatric symptoms. Eighteen patients had central nervous damage, 50 peripheral nervous damage. Central nervous damage was significantly more common in gunshot than explosion injuries (p = 0.015). Peripheral nervous damage was more common in explosion than gunshot injuries (p < 0.1). Fifty-one patients had polytrauma and 49 suffered from fractures. Therapy included surgical interventions (n = 56) and physiotherapy. Structured rehabilitation programs were often indicated., Conclusion: Specialized knowledge about war injuries and their management including hospital preparation and planning regarding infrastructure may be required anytime. Injuries include a broad variety of neurological, psychiatric and trauma surgical injuries. Therefore, an interdisciplinary approach is crucial.

We aimed to assess executive functioning in children after liver transplantation compared with healthy controls and in relation to real-life school performance using the PedsQL TM Cognitive Functioning Scale (CogPedsQL) and the Childrens' Color Trail Test (CCTT). One hundred and fifty five children (78f, median age 10.4 (1.2-18.3) years) underwent testing with CogPedsQL and/or CCTT 4.9 (0.1-17.0) years after transplantation. Results were compared to those of 296 healthy children (165f, median age 10.0 (2.0-18.0) years). Liver transplanted children displayed significantly reduced scores for cogPedsQL and CCTT1&2 compared to healthy controls. Overall, school performance was lower in patients compared to controls. In both patients and controls, results of CCTT2 and CogPedsQL correlated strongly with school performance. In contrast to controls, school performance in patients correlated with the level of maternal but not paternal primary education degree (r = -0.21, p = 0.03). None of the patient CCTT or CogPedsQL test results correlated with parental school education. Conclusion: CogPedsQL and CCTT 1&2 were easily applicable in children after OLT and revealed reduced executive functioning compared to controls. Results reflect real life school performance. The association of parental education with school performance is reduced in transplanted children, which possibly indicates the overriding impact of transplant-associated morbidity on cognitive outcomes.

Importance: Eating disorders (EDs) are common, serious psychiatric disorders on college campuses, yet most affected individuals do not receive treatment. Digital interventions have the potential to bridge this gap., Objective: To determine whether a coached, digital, cognitive behavior therapy (CBT) intervention improves outcomes for college women with EDs compared with referral to usual care., Design, Setting, and Participants: This cluster randomized trial was conducted from 2014 to 2018 at 27 US universities. Women with binge-purge EDs (with both threshold and subthreshold presentations) were recruited from enrolled universities. The 690 participants were followed up for up to 2 years after the intervention. Data analysis was performed from February to September 2019., Interventions: Universities were randomized to the intervention, Student Bodies-Eating Disorders, a digital CBT-guided self-help program, or to referral to usual care., Main Outcomes and Measures: The main outcome was change in overall ED psychopathology. Secondary outcomes were abstinence from binge eating and compensatory behaviors, as well as ED behavior frequencies, depression, anxiety, clinical impairment, academic impairment, and realized treatment access., Results: A total of 690 women with EDs (mean [SD] age, 22.12 [4.85] years; 414 [60.0%] White; 120 [17.4%] Hispanic; 512 [74.2%] undergraduates) were included in the analyses. For ED psychopathology, there was a significantly greater reduction in the intervention group compared with the control group at the postintervention assessment (β [SE], -0.44 [0.10]; d = -0.40; t1387 = -4.23; P < .001), as well as over the follow-up period (β [SE], -0.39 [0.12]; d = -0.35; t1387 = -3.30; P < .001). There was not a significant difference in abstinence from any ED behaviors at the postintervention assessment (odds ratio, 1.48; 95% CI, 0.48-4.62; P = .50) or at follow-up (odds ratio, 1.51; 95% CI, 0.63-3.58; P = .36). Compared with the control group, the intervention group had significantly greater reductions in binge eating (rate ratio, 0.82; 95% CI, 0.70-0.96; P = .02), compensatory behaviors (rate ratio, 0.68; 95% CI, 0.54-0.86; P < .001), depression (β [SE], -1.34 [0.53]; d = -0.22; t1387 = -2.52; P = .01), and clinical impairment (β [SE], -2.33 [0.94]; d = -0.21; t1387 = -2.49; P = .01) at the postintervention assessment, with these gains sustained through follow-up for all outcomes except binge eating. Groups did not differ in terms of academic impairment. The majority of intervention participants (318 of 385 participants [83%]) began the intervention, whereas only 28% of control participants (76 of 271 participants with follow-up data available) sought treatment for their ED (odds ratio, 12.36; 95% CI, 8.73-17.51; P < .001)., Conclusions and Relevance: In this cluster randomized clinical trial comparing a coached, digital CBT intervention with referral to usual care, the intervention was effective in reducing ED psychopathology, compensatory behaviors, depression, and clinical impairment through long-term follow-up, as well as realizing treatment access. No difference was found between the intervention and control groups for abstinence for all ED behaviors or academic impairment. Given its scalability, a coached, digital, CBT intervention for college women with EDs has the potential to address the wide treatment gap for these disorders., Trial Registration: ClinicalTrials.gov Identifier: NCT02076464.

Digital technology, which includes the collection, analysis, and use of data from a variety of digital devices, has the potential to reduce the prevalence of disorders and improve mental health in populations. Among the many advantages of digital technology is that it allows preventive and clinical interventions, both of which are needed to reduce the prevalence of mental health disorders, to be feasibly integrated into health care and community delivery systems and delivered at scale. However, the use of digital technology also presents several challenges, including how systems can manage and implement interventions in a rapidly changing digital environment and handle critical issues that affect population-wide outcomes, including reaching the targeted population, obtaining meaningful levels of uptake and use of interventions, and achieving significant outcomes. We describe a possible solution, which is to have an outcome optimization team that focuses on the dynamic use of data to adapt interventions for populations, while at the same time, addressing the complex relationships among reach, uptake, use, and outcome. We use the example of eating disorders in young people to illustrate how this solution could be implemented at scale. We also discuss system, practitioner-related, and other issues related to the adaptation of such an approach. Digital technology has great potential for facilitating the reduction of mental illness rates in populations. However, achieving this goal will require the implementation of new approaches. As a solution, we argue for the need to create outcome optimization teams, tasked with integrating data from various sources and using advanced data analytics and new designs to develop interventions/strategies to increase reach, uptake, use/engagement, and outcomes for both preventive and treatment interventions., (©C Barr Taylor, Josef I Ruzek, Ellen E Fitzsimmons-Craft, Shiri Sadeh-Sharvit, Naira Topooco, Ruth Striegel Weissman, Daniel Eisenberg, David Mohr, Andrea Graham, Corinna Jacobi, Brian Oldenburg. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.07.2020.)

Background: Eating problems are highly prevalent among young adults. Universities could be an optimal setting to prevent the onset of eating disorders through psychological intervention. As part of the World Mental Health-International College Student initiative, this systematic review and meta-analysis synthesizes data on the efficacy of eating disorder prevention programs targeting university students., Method: A systematic literature search of bibliographical databases (CENTRAL, MEDLINE, PsycINFO) for randomized trials comparing psychological preventive interventions for eating disorders targeting university students with psychoeducation or inactive controls was performed on October 22, 2019., Results: Twenty-seven studies were included. Thirteen (48.1%) were rated to have a low risk of bias. The relative risk of developing a subthreshold or full-blown eating disorder was incidence rate ratio = 0.62 (95% CI [0.44, 0.87], n c = 8, numbers-needed-to-treat [NNT] = 26.08; standardized clinical interviews only), indicating a 38% decrease in incidence in the intervention groups compared to controls. Small to moderate between-group effects at posttest were found on eating disorder symptoms (g = 0.35, 95% CI [0.24, 0.46], NNT = 5.10, n c = 26), dieting (g = 0.43, 95% CI [0.29, 0.57], NNT = 4.17, n c = 21), body dissatisfaction (g = 0.40, 95% CI [0.27, 0.53], NNT = 4.48, n c = 25), drive for thinness (g = 0.43, 95% CI [0.27, 0.59], NNT = 4.23, n c = 12), weight concerns (g = 0.33, 95% CI [0.10, 0.57], NNT = 5.35, n c = 13), and affective symptoms (g = 0.27, 95% CI [0.15, 0.38], NNT = 6.70, n c = 18). The effects on bulimia nervosa symptoms were not significant. Heterogeneity was moderate across comparisons., Discussion: Eating disorder prevention on campus can have significant, small-to-moderate effects on eating disorder symptoms and risk factors. Results also suggest that the prevention of subthreshold and full-syndrome eating disorders is feasible using such interventions. More research is needed to identify ways to motivate students to use preventive eating disorder interventions., Antecedentes: Los trastornos de la conducta alimentaria son altamente prevalentes entre los adultos jóvenes. Las universidades podrían ser un entorno óptimo para prevenir la aparición de trastornos alimentarios a través de la intervención psicológica. Como parte de la iniciativa World Mental Health-International College Student, esta revisión sistemática y meta-análisis sintetiza datos sobre la eficacia de los programas de prevención de trastornos alimentarios dirigidos a estudiantes universitarios. MÉTODO: Una búsqueda bibliográfica sistemática de datos bibliográficas (CENTRAL, MEDLINE, PsycINFO) para ensayos aleatorios que comparaban intervenciones preventivas psicológicas para trastornos alimentarios dirigidos a estudiantes universitarios con psicoeducación o controles inactivos fue realizada hasta el 22 de octubre de 2019., Resultados: Se incluyeron 27 estudios. Trece (48,1%) fueron calificados como de bajo riesgo de sesgo. El riesgo relativo de desarrollar un trastorno de la conducta alimentaria subclínico (parcial) o completo fue IRR = 0.62 (95% CI [0.44, 0.87], n c = 8, NNT = 26.08; sólo entrevistas clínicas estandarizadas), lo que indica una disminución del 38% en la incidencia en los grupos de intervención en comparación con los controles. Se encontraron efectos pequeños a moderados entre los grupos en la post-prueba en los síntomas del trastorno alimentario (g = 0.35, 95% CI [0.24, 0.46], NNT = 5.10, n c = 26), dieta (g = 0.43, 95% CI [0.29, 0.57], NNT = 4.17, n c = 21), insatisfacción corporal (g = 0.40, 95% CI [0.27, 0.53], NNT = 4.48, n c = 25), impulso por delgadez (g = 0.43, 95% CI [0.27, 0.59], NNT = 4.23, n c = 12), problemas de peso (g = 0.33, 95% CI [0.10, 0.57], NNT = 5.35, n c = 13) y síntomas afectivos (g = 0.27, 95% CI [0.15, 0.38], NNT = 6.70, n c = 18). Los efectos sobre los síntomas de la bulimia nervosa no fueron significativos. La heterogeneidad fue moderada en las comparaciones. DISCUSIÓN: La prevención de los trastornos de la conducta alimentaria en el campus universitario puede tener efectos significativos, de pequeños a moderados, sobre los síntomas del trastorno alimentario y los factores de riesgo. Los resultados también sugieren que la prevención de los trastornos alimentarios subclínicos o parciales y síndromes completos es factible utilizando tales intervenciones. Se necesita más investigación para identificar formas de motivar a los estudiantes a usar intervenciones preventivas para los trastornos de la conducta alimentaria., (© 2020 The Authors. International Journal of Eating Disorders published by Wiley Periodicals, Inc.)

Dry eye disease (DED) is a heterogenous disease of the ocular surface. Multiple pathogenetic factors are responsible for the disease process, but DED is generally linked to an increase in the osmolarity of the tear film and to inflammation of the ocular surface. The significance of inflammatory processes in DED is highlighted in the most recent definition of dry eye in the Dry Eye Workshop (DEWS). It is therefore critically important for the management of dry eye disease to understand the pathomechanisms and therapeutic options for the treatment of inflammatory processes. This review summarizes our current knowledge on Inflammation associated with DED and provides practical recommendations for the diagnosis and monitoring of the disease, as well as the use of currently available therapeutic options to counteract inflammation in DED., Competing Interests: U. Pleyer: Referent/Consultant für: Pharm Allergan GmbH, Santen GmbH, Théa Deutschland GmbH; G. Geerling: Referent/Consultant für Pharm Allergan GmbH, Santen GmbH, Shire, Tear Lab Inc, Tear Science, Théa Pharma GmbH; S. Schrader: Referent/Consultant für Santen GmbH und Tear Science; C. Jacobi: Referentin/Consultant für Théa Pharma GmbH, Santen GmbH und Shire Deutschland GmbH; F. Kimmich: Consultant für Santen GmbH; E. Messmer: Referentin/Consultant für: Pharm Allergan GmbH, Santen GmbH, Shire, Théa Deutschland GmbH., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Keratoconjunctivitis sicca is one of the most common ocular diseases and is associated with a considerable decrease in the quality of life. It is accompanied by symptoms of discomfort, tear film instability, hyperosmolarity of the tear film, inflammation of the ocular surface and neurosensory abnormalities. It is still not clear yet if the density of Langerhans cells in the central cornea can be used for objective evaluation of the inflammation in the tear film and the ocular surface., Patients and Methods: 47 patients (age 21 - 85 years, 13 male and 34 female patients) with moderate to severe keratoconjunctivitis sicca (according to the DEWS criteria severity level 2 - 3) were enrolled in this prospective, clinical trial. Patients were treated for 3 months with topical anti-inflammatory therapy with cyclosporine 0,05% eye drops twice daily. The following parameters were examined: OSDI Score, tear break-up time (TBUT), Schirmer test with anaesthesia, lid-parallel conjunctival folds (LIPCOF), in-vivo confocal microscopy with HRT II and RCM for evaluation of Langerhans cell density in the central cornea, visual acuity, tear film osmolarity and Meibomian gland dysfunction (MGD)., Results: After anti-inflammatory treatment, there was a significant reduction in the density of Langerhans cells (p ≤ 0.001**), an increase in TBUT (p ≤ 0.001**), as well as a significant decrease in tear film osmolarity (p ≤ 0.05*) and OSDI Score (p ≤ 0 001**). Visual acuity, MGD and Schirmer test did not change significantly., Conclusions: The results of this clinical trial show that topical anti-inflammatory therapy with cyclosporine A 0.05% eye drops in patients with moderate to severe keratoconjunctivitis sicca is effective in reducing inflammation of the ocular surface and the tear film, as well as in increasing the quality of life in these patients. Evaluation of Langerhans cell density in the central corneal epithelium by in vivo confocal microscopy is an effective objective diagnostic feature in monitoring anti-inflammatory therapy in patients with dry eye disease or other ocular surface pathologies., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Using data from a randomized controlled trial, we examined two different strategies to recruit participants for an indicated preventive intervention (StudentBodies-AN) for women at risk for anorexia nervosa and compared symptom severity and program utilization in participants recruited through each strategy., Method: We recruited participants by announcing the study (a) in lectures at universities and handing out screening questionnaires (face-to-face recruitment) and (b) through different media channels, and the participants completed the screening questionnaire on our study website (media-based recruitment). We compared symptom severity and program utilization between the two groups., Results: A total of 4,646 women (face-to-face: 3,741, media-based: 905) were screened and 168 women (face-to-face: 114, media-based: 54) were randomized to the intervention. We found a statistically and clinically significant association between recruitment strategy and symptom severity: Participants who were recruited through media were more likely to fulfill the inclusion criteria (40.6% vs. 13.3%; p < .001) and endorsed significantly more frequently core behaviors and attitudes of disordered eating (EDE global score: 2.72 vs. 2.17, p < .05; Weight Concerns Scale [WCS] score: 66.05 vs. 56.40, p < .05) at baseline than participants recruited face-to-face. Also, participants recruited through media were more likely to log onto the program (χ 2 = 5.06; p = .029) and accessed more of the intervention., Discussion: Recruitment through media seems both more feasible and suitable to reach individuals in need of indicative prevention, and should be part of a multimodal recruitment package. Future studies should be explicitly designed to investigate the impact of recruitment modality on reach and effectiveness including cost-effectiveness analyses., (© 2020 The Authors. International Journal of Eating Disorders published by Wiley Periodicals, Inc.)

Background: Day treatment programs for individuals with eating disorders (ED) have been the subject of research and are promoted as an alternative to inpatient treatment due to their therapeutic and economic advantages, but have not regularly been implemented in regular care., Purpose: We investigated the long-term effectiveness of a transdiagnostic combined eating disorder treatment program which consisted of an 8-week day treatment phase followed by an average of 19 sessions of outpatient treatment over an average of 39 weeks in a naturalistic setting., Methods: We accepted 148 patients with different diagnoses of eating disorders into our combined treatment program. We assessed weight, behavioral eating disorder symptoms and eating disorder related cognitions and attitudes at the beginning and the end of the day treatment phase and after 6, 12 and 26 months., Results: Over the course of the 8-week day treatment phase, patients with initial binge eating, purging and/or fasting behavior reduced these symptoms by 91%, 90% and, 86%. Patients who were underweight at baseline gained on average 1.05 BMI points (d = 0.76). In addition, eating disorder related cognitions and attitudes of all patients significantly improved with large effect sizes (d = 1.12). On average, all improvements remained stable during the follow-up period., Conclusions: Our findings add to the existing studies on day treatment and support previously found encouraging effects of treatment programs that combine day treatment and consecutive outpatient treatment for eating disorders., Level of Evidence: Level III, longitudinal cohort study.

Activins belong to the transforming growth factor (TGF)-β family of multifunctional cytokines and signal via the activin receptors ALK4 or ALK7 to activate the SMAD2/3 pathway. In some cases, activins also signal via the bone morphogenetic protein (BMP) receptor ALK2, causing activation of the SMAD1/5/8 pathway. In this study, we aimed to dissect how activin A and activin B homodimers, and activin AB and AC heterodimers activate the two main SMAD branches. We compared the activin-induced signaling dynamics of ALK4/7-SMAD2/3 and ALK2-SMAD1/5 in a multiple myeloma cell line. Signaling via the ALK2-SMAD1/5 pathway exhibited greater differences between ligands than signaling via ALK4/ALK7-SMAD2/3. Interestingly, activin B and activin AB very potently activated SMAD1/5, resembling the activation commonly seen with BMPs. As SMAD1/5 was also activated by activins in other cell types, we propose that dual specificity is a general mechanism for activin ligands. In addition, we found that the antagonist follistatin inhibited signaling by all the tested activins, whereas the antagonist cerberus specifically inhibited activin B. Taken together, we propose that activins may be considered dual specificity TGF-β family members, critically affecting how activins may be considered and targeted clinically.

Background: Digital health interventions (DHIs) are poised to reduce target symptoms in a scalable, affordable, and empirically supported way. DHIs that involve coaching or clinical support often collect text data from 2 sources: (1) open correspondence between users and the trained practitioners supporting them through a messaging system and (2) text data recorded during the intervention by users, such as diary entries. Natural language processing (NLP) offers methods for analyzing text, augmenting the understanding of intervention effects, and informing therapeutic decision making., Objective: This study aimed to present a technical framework that supports the automated analysis of both types of text data often present in DHIs. This framework generates text features and helps to build statistical models to predict target variables, including user engagement, symptom change, and therapeutic outcomes., Methods: We first discussed various NLP techniques and demonstrated how they are implemented in the presented framework. We then applied the framework in a case study of the Healthy Body Image Program, a Web-based intervention trial for eating disorders (EDs). A total of 372 participants who screened positive for an ED received a DHI aimed at reducing ED psychopathology (including binge eating and purging behaviors) and improving body image. These users generated 37,228 intervention text snippets and exchanged 4285 user-coach messages, which were analyzed using the proposed model., Results: We applied the framework to predict binge eating behavior, resulting in an area under the curve between 0.57 (when applied to new users) and 0.72 (when applied to new symptom reports of known users). In addition, initial evidence indicated that specific text features predicted the therapeutic outcome of reducing ED symptoms., Conclusions: The case study demonstrates the usefulness of a structured approach to text data analytics. NLP techniques improve the prediction of symptom changes in DHIs. We present a technical framework that can be easily applied in other clinical trials and clinical presentations and encourage other groups to apply the framework in similar contexts., (©Burkhardt Funk, Shiri Sadeh-Sharvit, Ellen E Fitzsimmons-Craft, Mickey Todd Trockel, Grace E Monterubio, Neha J Goel, Katherine N Balantekin, Dawn M Eichen, Rachael E Flatt, Marie-Laure Firebaugh, Corinna Jacobi, Andrea K Graham, Mark Hoogendoorn, Denise E Wilfley, C Barr Taylor. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 19.02.2020.)

Purpose: We assessed the static nasal valve angle with MR imaging in healthy subjects and evaluated the complex mechanism of nasal valve dynamics during physiologic and forced inspiration., Methods: In 17 healthy subjects, measurements of the static nasal valve angle were conducted on MR scans, using a TSE Axial T2-weighted sequence and a 3 mm slice thickness. The dynamic changes of nasal valve movement were detected using MR Cine-imaging techniques., Results: The static median angle of the nasal valve was found to be 28.6° with a range of 12.7°-39.3°. The median degree of nasal valve collapse during forced inspiration was 68% (range 20-99%) of the baseline (static nasal valve angle). In the moderately forced inspiration (3 s) the median nasal valve angle declined to 76% of the baseline angle (range 42-100%). In the physiologic or unforced inspiration, the median nasal valve angle was reduced to 86.3% of the baseline angle (range 52-100%)., Conclusion: MRI, as a non-invasive tool, is a reliable method for evaluation of the static nasal valve angle and for the illustration of the complex nasal valve dynamics.

Background: The majority of patients with advanced cancer develop cachexia, a weight loss syndrome that severely reduces quality of life and limits survival. Our understanding of the underlying mechanisms that cause the condition is limited, and there are currently no treatment options that can completely reverse cachexia. Several tumour-derived factors and inflammatory mediators have been suggested to contribute to weight loss in cachectic patients. However, inconsistencies between studies are recurrent. Activin A and interleukin 6 (IL-6) are among the best studied factors that seem to be important, and several studies support their individual role in cachexia development., Methods: We investigated the interplay between activin A and IL-6 in the cachexia-inducing TOV21G cell line, both in culture and in tumours in mice. We previously found that the human TOV21G cells secrete IL-6 that induces autophagy in reporter cells and cachexia in mice. Using this established cachexia cell model, we targeted autocrine activin A by genetic, chemical, and biological approaches. The secretion of IL-6 from the cancer cells was determined in both culture and tumour-bearing mice by a species-specific ELISA. Autophagy reporter cells were used to monitor the culture medium for autophagy-inducing activities, and muscle mass changes were evaluated in tumour-bearing mice., Results: We show that activin A acts in an autocrine manner to promote the synthesis and secretion of IL-6 from cancer cells. By inhibiting activin A signalling, the production of IL-6 from the cancer cells is reduced by 40-50% (up to 42% reduction on protein level, P = 0.0048, and 48% reduction on mRNA level, P = 0.0308). Significantly reduced IL-6 secretion (P < 0.05) from the cancer cells is consistently observed when using biological, chemical, and genetic approaches to interfere with the autocrine activin A loop. Inhibiting activin signalling also reduces the ability of the cancer cells to accelerate autophagy in non-cancerous cells (up to 43% reduced autophagy flux, P = 0.0006). Coherent to the in vitro data, the use of an anti-activin receptor 2 antibody in cachectic tumour-bearing mice reduces serum levels of cancer cell-derived IL-6 by 62% (from 417 to 159 pg/mL, P = 0.03), and, importantly, it reverses cachexia and counteracts loss of all measured muscle groups (P < 0.0005)., Conclusions: Our data support a functional link between activin A and IL-6 signalling pathways and indicate that interference with activin A-induced IL-6 secretion from the tumour has therapeutic potential for cancer-induced cachexia., (© 2019 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)