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Introduction: Schizophrenia-Spectrum-Disorders are associated with poor long-term outcome as well as disability and often severely affect the lives of patients and their families often from symptom onset. Up to 70% of first episode psychosis (FEP) patients suffer from comorbid substance use disorders (SUD). We aimed at studying the course of illness in FEP patients within evidence-based care, with and without comorbid SUD, to examine how decreased, remitted or persistent substance use impacted rates of a combined symptomatic and functional long-term recovery compared with patients without SUD., Methods: ACCESS III is an integrated care model for FEP or patients in the early phase of non-affective and affective psychotic disorders. Treatment trajectories of patients, who had been in ACCESS care for 1 year, with and without SUD were compared with regard to the course of illness and quality of life using Mixed Model Repeated Measures (MMRM) and recovery rates were compared using binary logistic regression. Change in substance use was coded as either persistent, decreased/remitted or no use., Results: ACCESS III was a prospective 1-year study ( N = 120) in patients aged 12-29 years. Of these, 74 (61.6%) had a comorbid SUD at admission. There were no group differences regarding the course of illness between patients with or without comorbid SUD or between patients with a substance abuse or substance dependence. The only outcome parameter that was affected by SUD was quality of life, with larger improvement found in the group without substance use ( p = 0.05) compared to persistent and remitted users. Using LOCF, 44 patients (48.9%) fulfilled recovery criteria at the endpoint; recovery did not differ based on substance use status., Discussion: SUD and especially substance dependence are common in psychotic disorders even in FEP patients. Evidence-based integrated care led to long-term improvement in patients with comorbid SUD and rate of recovery did not differ for patients with substance use., Competing Interests: ML: Consultant or speaker fees AstraZeneca, Bristol-Myers Squibb, Lilly Deutschland GmbH, Janssen Cilag GmbH, Lundbeck GmbH, Otsuka Pharma GmbH, Roche Deutschland Holding GmbH, Sanovi Aventis, and Trommsdorff GmbH & Co. KG. AK: Consultant or speaker fees from AstraZeneca, Bristol-Myers Squibb, Lilly Deutschland GmbH, Janssen Cilag GmbH, Lundbeck GmbH, Otsuka Pharma GmbH, and Roche Deutschland Holding GmbH. DL: Speaker fees Janssen Cilag GmbH. JG: Speaker fees from Lundbeck GmbH, Otsuka Pharma GmbH, and Janssen Cilag GmbH. DS received honoraria for lectures from, or has been an advisor to, Janssen GmbH, Lundbeck GmbH, Otsuka Pharma GmbH, Recordati, Rovi, and Takeda. The remaining 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 © 2023 Rühl, Lambert, Rohenkohl, Kraft, Daubmann, Schneider, Luedecke, Karow, Gallinat, Leicht and Schöttle.)

Introduction: Psychotic disorders have a significant impact on patients' lives and their families, and long-term treatment with individually tailored multimodal combinations of therapies is often required. Integrated care (IC) concepts such as the "Hamburg Model (ACCESS)" with a focus on psychotic disorders, includes different (therapeutic) components with pharmaco- and psychotherapy, family involvement, home treatment and the option of using a 24/7 crisis hotline. All components are offered by a therapeutically-oriented assertive community treatment (TACT) team in a need-adapted manner. So far, however, little is known about which specific components are regarded as especially relevant and helpful by the users of IC., Methods: Patients currently participating in IC completed a questionnaire as part of the continuous quality assurance study (ACCESS II) in which they were asked to rate the different components of treatment according to their relevance and helpfulness, considering the individual's unique experiences with IC and needs in mental health care. Furthermore, they were asked to make suggestions regarding additional helpful components of treatment., Results: Fifty patients participated in this survey (23% of the patients currently participating in the IC concept). For participants, the most helpful and important factors were having the same therapist in the long-term and the 24/7 crisis telephone. Additional components suggested by patients included more addiction-specific therapies and increased focus on vocational rehabilitation and integration., Conclusion: From the perspective of the users of IC, long-term care from a trusted therapist with whom there is a therapeutic relationship and the possibility to reach someone they already know from the TACT team 24/7 serves as the best basis for effective care, fostering trust, understanding, and open communication. In contrast, home treatment remains a relevant aspect of evidence-based care for people with severe mental illness, but perhaps surprisingly, is not viewed as the most important issue., 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 © 2023 Rohenkohl, Sowada, Lambert, Gallinat, Karow, Lüdecke, Rühl and Schöttle.)

Background: Patients with severe psychotic disorders exhibit a severely reduced quality of life (QoL) at all stages of the disease. Integrated care often led to an improvement in QoL. However, the specific mediators of QoL change are not yet well understood., Methods: The ACCESS II study is a prospective, long-term study investigating the effectiveness of an integrated care program for people with severe psychotic disorders (IC-TACT) that includes Therapeutic Assertive Community Treatment within a care network of in- and outpatient services at the University Medical Center Hamburg-Eppendorf, Germany. We examined longitudinal associations between QoL and the hypothesized mediators of change (i.e., negative symptoms, depression, and anxiety), using cross-lagged panel models., Results: The sample includes 418 severely ill patients treated in IC-TACT for at least 1 year. QoL increased, whereas symptom severity decreased significantly from baseline to 6-month follow-up ( p -values ≤ 0.001), and remained stable until 12-month follow-up. QoL and symptom severity demonstrated significant auto-correlated effects and significant cross-lagged effects from QoL at baseline to negative symptoms (6 months, β = -0.20, p < 0.001) to QoL (12 months, β = -0.19, p < 0.01) resulting in a significant indirect, mediated effect. Additionally, negative symptoms after 6 months had a significant effect on the severity of depression after 12 months ( β = 0.13, p < 0.05)., Conclusions: Negative symptoms appear to represent an important mechanism of change in IC-TACT indicating that improvement of QoL could potentially be achieved through optimized intervention on negative symptoms. Moreover, this may lead to a reduction in the severity of depression after 12 months.

Purpose: Studies on outcomes mapping Quality of Life (QoL) as patient-reported outcome over a longer period in severe psychotic disorders are scarce. However, such data would be particularly important for structuring, implementing and operating effective and efficient care models and for promoting satisfaction with care, service engagement and adherence., Methods: The ACCESS II study is a prospective long-term study of an integrated care model for people with severe psychotic disorders. The model includes Therapeutic Assertive Community Treatment within a cross-sectoral and interdisciplinary network. This publication analyses the course of QoL assessed with the Q-LES-Q-18 using a mixed model for repeated measures., Results: Mapping the course of QoL in N = 329 participants, there is a significant increase in the first 6 weeks of treatment (early course). Comparison to a published norm show significant lower QoL for severe psychotic disorders. The variable having a traumatic event before the age of 18 was significantly negatively associated with QoL. A decrease in the severity of depressive as well as in positive symptomatology in the first six weeks after admission was associated with increase of QoL., Conclusion: Results indicate that the overall symptom burden at time of inclusion is not decisive for the perceived QoL in the long-term course while the reduction in the severity of depressive and positive symptoms is important. This means focusing even more on the treatment of depressive symptoms and include traumatherapeutic aspects in the long-term treatment of severe psychotic disorders if needed., Trail Registration: ClinicalTrials.gov (identifier: NCT01888627)., (© 2022. The Author(s).)

Nanobodies (VHHs) are the single variable immunoglobulin domains of heavy chain antibodies (hcAbs) that naturally occur in alpacas and other camelids. The two variable domains of conventional antibodies typically interact via a hydrophobic interface. In contrast, the corresponding surface area of nanobodies is hydrophilic, rendering these single immunoglobulin domains highly soluble, robust to harsh environments, and exceptionally easy to format into bispecific reagents. In homage to Geoffrey Burnstock, the pioneer of purinergic signaling, we provide a brief history of nanobody-mediated modulation of purinergic signaling, using our nanobodies targeting P2X7 and the NAD + -metabolizing ecto-enzymes CD38 and ARTC2.2 as examples., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Oncologic imaging is a key for successful cancer treatment. While the quality assurance (QA) of image acquisition protocols has already been focussed, QA of reading and reporting offers still room for improvement. The latter was addressed in the context of a prospective multicentre trial on fluoro-deoxyglucose (FDG)-positron-emission tomography (PET)/CT-based chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC)., Material and Methods: An expert panel was prospectively installed performing blinded reviews of mediastinal NSCLC involvement in FDG-PET/CT. Due to a high initial reporting inter-observer disagreement, the independent data monitoring committee (IDMC) triggered an interventional harmonisation process, which overall involved 11 experts uttering 6855 blinded diagnostic statements. After assessing the baseline inter-observer agreement (IOA) of a blinded re-review (phase 1), a discussion process led to improved reading criteria (phase 2). Those underwent a validation study (phase 3) and were then implemented into the study routine. After 2 months (phase 4) and 1 year (phase 5), the IOA was reassessed., Results: The initial overall IOA was moderate (kappa 0.52 CT; 0.53 PET). After improvement of reading criteria, the kappa values improved substantially (kappa 0.61 CT; 0.66 PET), which was retained until the late reassessment (kappa 0.71 CT; 0.67 PET). Subjective uncertainty was highly predictive for low IOA., Conclusion: The IOA of an expert panel was significantly improved by a structured interventional harmonisation process which could be a model for future clinical trials. Furthermore, the low IOA in reporting nodal involvement in NSCLC may bear consequences for individual patient care., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In 783 patients from age 38 to 83 aspiration cytology of the endometrium was carried out and compared to microscopic findings of the endometrium from the curettages. The samples were obtained from women with post-menopausal and pre-menopausal bleeding and from women without bleeding prior to hysterectomy for various indications. In 49.% of the cases adenocarcinoma of the endometrium was detected, and in 4.2% of the cases pre-cancerous lesions such as adenomatous or atypical glandular hyperplasia of the endometrium and of the endocervix were observed.

Cultivation parameters for the production of five lymphokines, granulocyte-macrophage colony stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), interleukin 2 (IL-2), macrophage cytotoxicity factor (MCF), and macrophage migration inhibitory factor (MIF) from human spleen cells or peripheral blood lymphocytes were optimized. Cultivation was done in bioreactors containing up to 200 ml of medium, usually serum-free. The reactors were equipped with surface aeration facilities, stirrers and oxygen electrodes. Whereas stirring speed alone did not influence the yields of lymphokines, good aeration was especially beneficial for high IL-2 yields. However, all lymphokines were also produced under anaerobic conditions. The concentration of the mitogen concanavalin A was mainly critical for optimal IL-2 release. Optimal cell concentrations varied from 5 X 10(6)/ml (for GM-GSF and MCF) to 10 X 10(6)/ml (for IL-2 and IFN-gamma). It was possible to increase the yields of individual lymphokines 3 to 10-fold per batch of lymphocytes by a reinduction procedure which involved a change of medium and mitogen every 24 hrs. Reinduction was possible up to 4 times, especially when serum was present in the culture media.

Based on a stress analysis of bow-tie optical fibers, a mechanism for true single-mode single-polarization operation of bow-tie optical fibers is presented. The y-polarized mode can have a loss of the order of 10 dB/m, while the x-polarized mode remains well confined and without loss.