Pharmacodynamic Modeling of Anti-Cancer Activity of Tetraiodothyroacetic Acid in a Perfused Cell Culture System

Unmodified or as a poly[lactide-co-glycolide] nanoparticle, tetraiodothyroacetic acid (tetrac) acts at the integrin αvβ3 receptor on human cancer cells to inhibit tumor cell proliferation and xenograft growth. To study in vitro the pharmacodynamics of tetrac formulations in the absence of and in conjunction with other chemotherapeutic agents, we developed a perfusion bellows cell culture system. Cells were grown on polymer flakes and exposed to various concentrations of tetrac, nano-tetrac, resveratrol, cetuximab, or a combination for up to 18 days. Cells were harvested and counted every one or two days. Both NONMEM VI and the exact Monte Carlo parametric expectation maximization algorithm in S-ADAPT were utilized for mathematical modeling. Unmodified tetrac inhibited the proliferation of cancer cells and did so with differing potency in different cell lines. The developed mechanism-based model included two effects of tetrac on different parts of the cell cycle which could be distinguished. For human breast cancer cells, modeling suggested a higher sensitivity (lower IC50) to the effect on success rate of replication than the effect on rate of growth, whereas the capacity (Imax) was larger for the effect on growth rate. Nanoparticulate tetrac (nano-tetrac), which does not enter into cells, had a higher potency and a larger anti-proliferative effect than unmodified tetrac. Fluorescence-activated cell sorting analysis of harvested cells revealed tetrac and nano-tetrac induced concentration-dependent apoptosis that was correlated with expression of pro-apoptotic proteins, such as p53, p21, PIG3 and BAD for nano-tetrac, while unmodified tetrac showed a different profile. Approximately additive anti-proliferative effects were found for the combinations of tetrac and resveratrol, tetrac and cetuximab (Erbitux), and nano-tetrac and cetuximab. Our in vitro perfusion cancer cell system together with mathematical modeling successfully described the anti-proliferative effects over time of tetrac and nano-tetrac and may be useful for dose-finding and studying the pharmacodynamics of other chemotherapeutic agents or their combinations

Diagnostic barriers for somatic symptom disorders in primary care: study protocol for a mixed methods study in Germany

Introduction Somatoform or somatic symptom disorders ((S)SD) are common and have a negative impact on the patients' health-related quality of life, healthcare use and costs. In primary care, which is central to the management of (S) SD, diagnosis and treatment tend to be delayed. There is a significant lack of evidence regarding the barriers in the diagnostic process of (S) SD in primary care and how interventions should be tailored to address them. The aim of this study is to analyse the diagnostic process in primary care that results in the diagnosis or non-diagnosis of a (S) SD. Methods and analysis This mixed methods study will investigate the topic with qualitative methods, subsequently proceeding to a quantitative phase where the initial results will be validated and/or generalised. First, focus groups will explore meanings and patterns, inconsistencies and conflicts in general practitioners' (GPs) thoughts and behaviours when diagnosing (S) SD. Second, the results of these focus groups will be used to develop interview guidelines for subsequent face-to-face interviews. Patients and their treating GPs will be interviewed separately on how they experience the history of illness, the diagnostic process and treatment. Third, based on the results of the first two study parts, a questionnaire will be derived and a nationwide survey among German GPs will be conducted, quantifying the barriers and difficulties identified before. Ethics and dissemination Ethics approval was obtained from the Ethics Committee of the Hamburg Medical Association, Germany (approval number PV4763). The results of this study will be disseminated through conference presentation and publications in peer-reviewed journals

The cross-sectional Relationship between specific and general Impact Factors in psychodynamic and behavioral Psychotherapy Sessions

Biel H, Algner-Herzmann D, Hennig T, Krott NR, Loewe B, Reininger KM. The cross-sectional Relationship between specific and general Impact Factors in psychodynamic and behavioral Psychotherapy Sessions. In: Deutscher Kongress für Psychosomatische Medizin und Psychotherapie vom 16. bis 18. Juni 2021. Zeitschrift für Psychosomatische Medizin und Psychotherapie . Vol 67. Göttingen: Vandenhoeck & Ruprecht; 2021: 158

How to assess common somatic symptoms in large-scale studies:A systematic review of questionnaires

Objective: Many questionnaires for assessment of common somatic symptoms or functional somatic symptoms are available and their use differs greatly among studies. The prevalence and incidence of symptoms are partially determined by the methods used to assess them. As a result, comparison across studies is difficult. This article describes a systematic review of self-report questionnaires for somatic symptoms for use in large-scale studies and recommends two questionnaires for use in such studies.Methods: A literature search was performed in the databases Medline, PsycINFO and EMBASE. Articles that reported the development, evaluation, or review of a self-report somatic symptom measure were included. Instrument evaluation was based on validity and reliability, and their fitness for purpose in large scale studies, according to the PhenX criteria.Results: The literature search identified 40 questionnaires. The number of items within the questionnaires ranged from 5 to 78 items. In 70% of the questionnaires, headaches were included, followed by nausea/upset stomach. (65%), shortness of breath/breathing trouble (58%), dizziness (55%), and (low) back pain/backaches (55%). Data on validity and reliability were reported and used for evaluation.Conclusion: Questionnaires varied regarding usability and burden to participants, and relevance to a variety of populations and regions. Based on our criteria, the Patient Health Questionnaire-15 and the Symptom Checklist-90 somatization scale seem the most fit for purpose for use in large-scale studies. These two questionnaires have well-established psychometric properties, contain relevant symptoms, are relatively short, and are available in multiple languages. (C) 2013 Elsevier Inc. All rights reserved.</p

Psychosomatic medicine in primary care : influence of training

BACKGROUND: General practitioners (GPs) are often confronted with patients presenting somatic symptoms presumed to be decisively modulated by psychosocial factors. OBJECTIVES: We aimed to explore GPs' reported clinical routine in dealing with these patients according to the GPs' level of training in psychosomatic medicine. METHODS: A structured postal questionnaire survey was conducted among all Austrian GPs with a standardized training background in psychosomatic medicine (three levels of training; duration between one and six years) as well as in a random national sample of Austrian GPs without such training, resulting in four study subgroups. RESULTS: Respondents estimated that between 20% and 40% of their patients presenting somatic symptoms need psychosocial factors to be addressed. Study subgroups differed significantly concerning their reported diagnostic and therapeutic routine behavior patterns. Some diagnostic approaches such as clarification of lay etiology increased linearly with the level of training. The proportion of patients receiving corresponding treatment in the GP's own practice was also reported to increase with the level of training (no training: 35%, levels one and two: 46%, level three: 54%), although all subgroups estimated that over 20% of patients do not receive any corresponding treatment. CONCLUSIONS: Results point at the clinical relevance of a general training in psychosomatic medicine in primary care. They also suggest specific training effects that need to be substantiated in observational studies

Affective mentalization as beliefs about the controllability and usefulness of emotions. Validation of a German language version of the Emotion Beliefs Questionnaire

Biel HM, Loewe B, Briken P, et al. Affektive Mentalisierung als wahrgenommene Kontrollierbarkeit und Nützlichkeit von Emotionen. Validierung einer deutschsprachigen Version des Emotion Beliefs Questionnaire. Psychotherapie. 2022.Background: Instruments for the investigation of mentalization should consider and specify the multidimensionality of this construct. Indicative for the pole of affective mentalization is, on the one hand, a perceived controllability of emotions due to the understanding of one's own and others' emotions and on the other hand, a perceived usefulness of emotions due to the attributed meaningfulness of one's own and others' emotions. Perceived controllability and usefulness of positive and negative emotions are assessed with the 16 items of the English language Emotion Beliefs Questionnaire (EBQ; Becerra et al. 2020) in a self-report.Objective: The aim of the present study was to develop a German language version of the EBQ as a survey instrument for affective mentalization ability and to determine its reliability and validity.Material and methods: A total of 104 psychotherapists in training and further education as well as students answered the German language EBQ, which we translated according to the translation guidelines of the European Social Survey, as part of an anonymous online survey. We conducted an exploratory factor analysis and determined internal consistencies and concurrent validities with respect to related constructs.Results: As in the original validation study, the EBQ shows a three-factorial structure and good internal consistency of alpha = 0,87 in the overall scale. Furthermore, associations between the perception of positive and negative emotions as uncontrollable and useless (high EBQ scores) and lower emotion regulation and higher psychopathological symptoms (concurrent validity) are evident.Conclusion: The findings are consistent with the results of the original validation study and suggest that the EBQ is also recommended in the German version. Theoretically justified and empirically tested (see online supplementary), the EBQ appears to be a suitable method for assessing affective mentalization.Hintergrund Instrumente zur Untersuchung von Mentalisierung sollten die Multidimensionalität dieses Konstrukts berücksichtigen und spezifizieren. Indikativ für den Pol der affektiven Mentalisierung sind einerseits aufgrund des Verständnisses für eigene und fremde Emotionen eine wahrgenommene Kontrollierbarkeit von Emotionen, andererseits aufgrund der attribuierten Bedeutsamkeit eigener und fremder Emotionen eine wahrgenommene Nützlichkeit von Emotionen. Die wahrgenommene Kontrollierbarkeit und Nützlichkeit positiver und negativer Emotionen wird mit den 16 Items des englischsprachigen Emotion Beliefs Questionnaire (EBQ; Becerra et al. 2020) im Selbstbericht erfasst. Ziel der Studie Ziele der vorliegenden Studie waren es, eine deutschsprachige Version des EBQ als Erhebungsinstrument für affektive Mentalisierungsfähigkeit zu entwickeln sowie deren Reliabilität und Validität zu ermitteln. Material und Methoden Psychotherapeut:innen in Aus- und Weiterbildung sowie Studierende (n = 104) beantworteten den von uns in Anlehnung an die Translation Guidelines des European Social Survey übersetzten deutschsprachigen EBQ als Teil einer anonymen Online-Befragung. Wir führten eine explorative Faktorenanalyse durch und bestimmten interne Konsistenzen sowie konkurrente Validitäten in Bezug auf verwandte Konstrukte. Ergebnisse Wie in der Originalvalidierungsstudie zeigen sich eine dreifaktorielle Struktur des EBQ sowie eine gute interne Konsistenz von α = 0,87 in der Gesamtskala. Weiterhin zeigen sich Zusammenhänge zwischen der Wahrnehmung von positiven und negativen Emotionen als unkontrollierbar und nutzlos (hohe EBQ-Werte) und einer geringeren Emotionsregulation sowie höheren psychopathologischen Symptomen (konkurrente Validität). Schlussfolgerung Die Befunde decken sich mit den Ergebnissen der originalen Validierungsstudie und legen nahe, dass der EBQ auch in der deutschen Version zu empfehlen ist. Theoretisch begründet und empirisch überprüft (siehe Online-Appendix) erscheint der EBQ als ein geeignetes Verfahren zur Erhebung affektiver Mentalisierung

Longitudinal development of depression and anxiety during COVID-19 pandemic in Germany: Findings from a population-based probability sample survey

The stress response to the COVID-19 pandemic might differ between early and later stages. Longitudinal data on the development of population mental health during COVID-19 pandemic is scarce. We have investigated mental health trajectories and predictors for change in a probability sample of the general population in Germany at the beginning and after 6 months of the pandemic. We conducted a longitudinal survey in a population-based probability sample of German adults. The current study analyzed data from a first assessment in May 2020 (T1; N = 1,412) and a second in November 2020 (T2; N = 743). Mental health was assessed in terms of anxiety and depression using the Patient Health Questionnaire-4 (PHQ-4). Mental health outcomes at T1 were compared with PHQ-4 norm data. Trajectories over time were investigated based on outcome classifications of PHQ-4 scores. Predictors of mental health outcomes and change were identified using multiple regression analysis. In spring 2020, participants showed significantly higher PHQ-4 scores as compared to the norm data, however, overall anxiety and depression remained low also 6 months later. 6.6% of respondents showed a mental health deterioration in autumn 2020, entering subclinical and clinical ranges, outweighing the proportion of people with improved outcomes. Sociodemographic variables associated with mental distress at T1 were mainly not predictive for change at T2. Even under prolonged pandemic-related stress, mental health remained mainly stable in the general population. Further development of the considerable subgroup experiencing deterioration of depression and anxiety should be monitored, in order to tailor prevention and intervention efforts

Effects of a Psychological Internet Intervention in the Treatment of Mild to Moderate Depressive Symptoms: Results of the EVIDENT Study, a Randomized Controlled Trial

Klein JP, Berger T, Schroeder J, et al. Effects of a Psychological Internet Intervention in the Treatment of Mild to Moderate Depressive Symptoms: Results of the EVIDENT Study, a Randomized Controlled Trial. Psychotherapy and Psychosomatics. 2016;85(4):218-228.Background: Mild to moderate depressive symptoms are common but often remain unrecognized and treated inadequately. We hypothesized that an Internet intervention in addition to usual care is superior to care as usual alone (CAU) in the treatment of mild to moderate depressive symptoms in adults. Methods: This trial was controlled, randomized and assessor-blinded. Participants with mild to moderate depressive symptoms (Patient Health Questionnaire, PHQ-9, score 5-14) were recruited from clinical and non-clinical set-tings and randomized to either CAU or a 12-week Internet intervention (Deprexis) adjunctive to usual care. Outcomes were assessed at baseline, 3 months (post-assessment) and 6 months (follow-up). The primary outcome measure was self-rated depression severity (PHQ-9). The main analysis was based on the intention-to-treat principle and used linear mixed models. Results: A total of 1,013 participants were randomized. Changes in PHQ-9 from baseline differed significantly between groups (t(825) = 6.12, p < 0.001 for the main effect of group). The post-assessment between-group effect size in favour of the intervention was d = 0.39 (95% CI: 0.13-0.64). It was stable at follow-up, with d = 0.32 (95% CI: 0.06-0.69). The rate of participants experiencing at least minimally clinically important PHQ-9 change at the post-assessment was higher in the intervention group (35.6 vs. 20.2%) with a number needed to treat of 7 (95% CI: 5-10). Conclusions: The Internet intervention examined in this trial was superior to CAU alone in reducing mild to moderate depressive symptoms. The magnitude of the effect is clinically important and has public health implications. (C) 2016 S. Karger AG, Base