Corrigendum: Individuals under voluntary treatment with sexual interest in minors: what risk do they pose?

[This corrects the article DOI: 10.3389/fpsyt.2023.1277225.].

The relationship between bullying victimization and impairment in personality functioning in a clinical adolescent sample.

Problematic interpersonal relationships may represent both, a risk factor for the development or trigger of personality disorder (PD) symptoms and its consequences. Since peer relationships become more and more important in adolescence, the current study explores the cross-sectional association between recent bullying experiences and levels of impairment in personality functioning according to the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) alternative model of personality disorders (AMPD; Criterion A) in help-seeking adolescents (N = 493). Logistic and multiple regression analyses revealed that patients who were frequently bullied in the past 3 months (i.e., at least once a week) were more likely to reach the diagnostic threshold for PD according to the AMPD (OR = 1.71, p = .025) and showed higher levels of impairment in identity (ß = .41, p < .001), empathy (ß = .26, p = .002), and intimacy (ß = .30, p = .001), but not self-direction, compared to patients who did not report any bullying experiences. Occasional bullying in the past 3 months (i.e., every few weeks) was neither associated with a greater likelihood to reach the diagnostic threshold for PD nor with greater impairments in identity, self-direction, empathy, or intimacy compared to no bullying. While the current study provides support for a correlation between bullying experiences and personality dysfunction (particularly in the elements identity and intimacy), longitudinal research is needed to clarify whether experiences of bullying cause or trigger personality dysfunction or/and vice versa. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Fostering resilience and well-being in emerging adults with adverse childhood experiences: study protocol for a randomized controlled trial to evaluate the FACE self-help app.

BACKGROUND: Adverse childhood experiences (ACE) are linked to an increased risk of psychological disorders and lower psychosocial functioning throughout life. This study aims to evaluate the FACE self-help app, designed to promote resilience and well-being in emerging adults with a history of ACE. The app is based on cognitive-behavioural principles and consists of two thematic components: (1) self- and emotion regulation (SER) and (2) social skills and biases in social information processing (SSIP). METHODS: The efficacy of the app will be tested through a single-centre, two-arm randomized controlled trial, comparing an active intervention group against a waiting list control group. The active group is divided into two subgroups, in which the two components are delivered in a different order to investigate differential effects in a crossover design. Up to 250 emerging adults aged 18 to 25 years with a history of ACE from a general population cohort study will be recruited. The primary objective is to test the efficacy of the app in improving resilience (primary outcome) and well-being (co-primary outcome) compared to a waiting list control group and to examine the stability of these effects. The secondary objectives include testing the efficacy of the app in improving the secondary outcomes, i.e., self-efficacy in managing emotions, problem solving, fear of evaluation, social avoidance, and self-esteem; examining the differential effects of the two components; and assessing the effect of the app on real-life data on resilience, affective states, distress in social interactions and coping strategies. Furthermore, the study will investigate potential moderators (e.g. ACE severity) and mediators of intervention outcomes (e.g. self-efficacy in managing emotions). DISCUSSION: The results will provide insights into the efficacy of the self-help intervention as well as mediators and moderators of outcomes. Furthermore, results will extend the existing knowledge by testing the differential effects of the SER and SSIP component on the outcomes. Findings can inform improvements to the FACE app and the development of other interventions for this target group and assess its potential as a scalable, low-threshold intervention to support emerging adults with a history of ACE in their transition to adulthood. TRIAL REGISTRATION NUMBER: NCT05824182.

Mediators of Outcome in Trauma-Focused Psychotherapy with Youth: A Systematic Review.

This article aimed to provide a systematic narrative synthesis of existing studies on the mediators of change in psychotherapy with adolescents (10-19 years) and transition age youth (TAY) (20-29 years) who have experienced trauma-related symptoms or posttraumatic disorder. Additionally, we were interested in identifying psychotherapy-, trauma type-, and clients' age- and gender-specific mediators of treatment outcome. Following the preferred reporting items for systematic reviews and meta-analyses, a total of 3,723 studies published in PubMed and PsycINFO databases were screened against inclusion criteria, revealing 15 eligible studies. No studies with only TAY were found; therefore, all results were limited to therapy with adolescents. Cognitive mediators were tested in 66% of selected studies, followed by parents/family-related, mental-health-related, therapy-related, and behavioral mediators. Moderate evidence was found for posttraumatic cognitions, whereas therapeutic alliance seemed to be a promising candidate for future research. Striking absence of non-cognitive-behavioral therapy interventions, emotional and adolescent-specific mediators, as well as studies with males and in non-Western societies was evident. Future original studies would benefit from applying methodological rigor in respect to mediation testing.

Diurnal variation of cardiac autonomic activity in adolescent non-suicidal self-injury.

Heart rate (HR) and vagally mediated heart rate variability (HRV) are two distinct biomarkers of cardiac autonomic activity. Decreased cardiac vagal activity (or decreased HRV) in particular has been linked with impairments in the functional flexibility of the central autonomic network (CAN), resulting in impaired stress and emotion regulatory capacities. Decreased HRV is widely used as trait marker of psychopathology. Repetitive engagement in non-suicidal self-injury (NSSI) in adolescence correlates with both deficits in stress and emotion regulation, as well as decreased HRV. Existing research has, however, focused on short-term recordings of HR and HRV under resting and phasic conditions. In this study, we examined whether diurnal variation of cardiac autonomic activity, indexed by cosinor parameters of HR and HRV derived from 48 h of ambulatory ECG recording under natural conditions over a weekend, are altered in female adolescents with NSSI disorder compared to controls (HC; N = 30 per study group). Several important confounds, including physical activity, were controlled for. Female adolescents with NSSI show higher rhythm-adjusted 24 h mean levels and greater respective amplitude of HR, as well as lower rhythm-adjusted 24 h mean levels and smaller respective amplitude of HRV. Peak levels in both HR and HRV in the NSSI group were reached approximately 1 h later compared to HC. Severity of exposure to early life maltreatment might be linked with altered amplitudes of 24 h HR and HRV. Diurnal rhythms of cardiac autonomic activity might hold promise as objective indicators of disordered stress and emotion regulation in developmental psychopathology, and as such should be investigated in future studies with rigorous assessment and control of potential confounds.

Individuals under voluntary treatment with sexual interest in minors: what risk do they pose?

Child Sexual Abuse (CSA) and the production, use, and distribution of Child Sexual Abuse Material (CSAM) are key threats to children's mental health. From the perspective of indicated prevention, it can be assumed that some persons with a sexual interest in children commit such unreported crimes. Accordingly, the German Network kein Täter werden (meaning do not offend) has implemented a confidential treatment service for persons with a sexual interest in minors who voluntarily seek therapy, might or might not have offended but have not yet been detected or have fulfilled all legal requirements (here referred to as non-forensic individuals). However, this offer has been questioned for investing resources in a group which critics consider as low risk. The following study addresses the question of recidivism risks for CSA or viewing CSAM among non-forensic individuals. We found significantly higher rates of CSA/CSAM in our participants' history compared to a German study on a representative sample of males. Regarding CSAM, the recidivism rate of 39% was found to be 11 times higher than the expected recidivism rate based on previous publications. Regarding CSA, the recidivism rate of 14% was not significantly different from the expected rate reported for subjects with a conviction for a sexual contact offense. Among various risk instruments, only the CPORT with CASIC rating was able to predict CSA (AUC = 0.69, 95% CI = 0.55, 0.82) and CSAM (AUC = 0.63, 95% CI = 0.53, 0.73) among individuals with a history of CSAM, but with poor discrimination. We conclude that a large proportion of our sample poses a substantial risk and therefore treatment resources are well invested. However, further studies are needed to improve risk assessment among non-forensic clients.

Fluctuation of Acquired Resistance Mutations and Re-Challenge with EGFR TKI in Metastatic NSCLC: A Case Report.

Osimertinib has become the preferred first-line therapy for epidermal growth factor receptor (EGFR) mutation-positive metastatic non-small cell lung cancer (NSCLC) in recent years. Originally, it was approved for second-line treatment after epidermal growth factor receptor EGFR tyrosine kinase inhibitors (TKIs) of the first and second generations had failed and EGFR T790M had emerged as a mode of resistance. Osimertinib itself provokes a wide array of on- and off-target molecular alterations that can limit therapeutic success. Liquid biopsy ctDNA (circulating tumor DNA) analysis by hybrid capture (HC) next-generation sequencing (NGS) can help to identify alterations in a minimally invasive way and allows for the detection of common as well as rare resistance alterations. We describe a young female patient who was initially diagnosed with metastatic EGFR L858R-positive NSCLC. She received EGFR TKI therapy at different timepoints during the course of the disease and developed sequential EGFR resistance alterations (EGFR T790M and C797S). In the course of her disease, resistance alteration became undetectable, and the tumor was successfully rechallenged with the original first-generation EGFR TKI as well as osimertinib and altogether showed prolonged response despite a prognostically negative TP53 alteration. To date, the patient has been alive for more than seven years, though initially diagnosed with a heavy metastatic burden.

Totally tubeless, tubeless, and tubed percutaneous nephrolithotomy for treating kidney stones.

BACKGROUND: Percutaneous nephrolithotomy (PNL) is the standard of care for removing large kidney stones (> 2 cm). Once the procedure is complete, different exiting strategies exist to manage the percutaneous tract opening, including placement of an external nephrostomy tube, placement of an internal ureteral stent, or no external or internal tube. The decision to place or not place a tube is handled differently among clinicians and may affect patient outcomes. OBJECTIVES: To assess the effects of tubeless PNL (with ureteral stenting), totally tubeless PNL (without ureteral stenting or nephrostomy), and standard PNL (nephrostomy only) for the treatment of kidney stones in adults. SEARCH METHODS: We performed a systematic literature search in multiple biomedical databases (CENTRAL, MEDLINE, Embase, Web of Science), as well as in two clinical trial registries. We also handsearched reference lists of relevant publications and conference proceedings. We applied no language restrictions. The latest search update was conducted in September 2022. SELECTION CRITERIA: We included randomized controlled and quasi-randomized controlled trials of adult patients who received tubeless, totally tubeless, or standard PNL for treating kidney stones. We defined tubeless PNL as no nephrostomy tube, but ureteral stenting, while totally tubeless PNL meant no nephrostomy tube or ureteral stenting. Both interventions were compared to standard PNL with placement of a nephrostomy tube (only). We considered access tubes of any sizes. We only considered unilateral PNL with single-tract access. There were no exclusions on stone composition, size, or location. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature, extracted data, assessed risk of bias, and rated the certainty of evidence using GRADE. Primary outcomes were severe adverse events and postoperative pain, and secondary outcomes were operating time, length of hospital stay, and stone-free rate. We used the random-effects model for meta-analysis. MAIN RESULTS: We included 10 studies in the review. Participant age varied among studies, ranging from 20 to 60 years. Detailed information on stone characteristics was rarely presented. Tubeless PNL versus standard PNL We are very uncertain whether there is a difference in severe adverse events (SAEs) between tubeless PNL and standard PNL (risk ratio (RR) 1.53, 95% confidence interval (CI) 0.14 to 16.46; I2 = 42%; 2 studies, 46 participants; very low-certainty evidence). Tubeless PNL may have little to no effect on pain on postoperative day one (mean difference (MD) 0.56 lower, 95% CI 1.34 lower to 0.21 higher; I2 = 84%; 4 studies, 186 participants; low-certainty evidence), and probably results in little to no difference in operating room time (MD 0.40 longer (in minutes), 95% CI 4.82 shorter to 5.62 longer; I2 = 0%; 3 studies, 81 participants; moderate-certainty evidence). Tubeless PNL may reduce length of hospital stay (MD 0.90 shorter, 95% CI 1.45 shorter to 0.35 shorter; I2 = 84%; 6 studies, 238 participants; low-certainty evidence). We are very uncertain of the effect of tubeless PNL on blood transfusions (RR 0.64, 95% CI 0.16 to 2.52; I2 = 0%; 4 studies, 161 participants; very low-certainty evidence), sepsis or fever (RR 0.50, 95% CI 0.05 to 4.75; I2 = not applicable; 2 studies, 82 participants; very low-certainty evidence), or readmissions (RR 1.00, 95% CI 0.07 to 14.21; I2 = not applicable, 1 study, 24 participants; very low-certainty evidence). Totally tubeless versus standard PNL Totally tubeless PNL may result in lower SAE rates (RR 0.49, 95% CI 0.19 to 1.25; I2 = 0%; 2 studies, 174 participants; low-certainty evidence) and pain on postoperative day one (MD 3.60 lower, 95% CI 4.24 lower to 2.96 lower; I2 = Not applicable; 1 study, 50 participants; low-certainty evidence). Totally tubeless PNL may result in little to no difference in operating room time (MD 6.23 shorter (in minutes), 95% CI 14.29 shorter to 1.84 longer; I2 = 72%; 2 studies, 174 participants; moderate-certainty evidence) and sepsis or fever (RR 0.33, 95% CI 0.01 to 7.97; I2 = not applicable; 1 study, 90 participants; low-certainty evidence). Totally tubeless PNL likely shortens the length of hospital stay (MD 1.55 shorter, 95% CI 1.82 shorter to 1.29 shorter; I2 = 0%; 4 studies, 274 participants; moderate-certainty evidence). We are very uncertain of the effect of totally tubeless PNL on blood transfusions (RR 0.62, 95% CI 0.26 to 1.48; I2 = 0%; 4 studies, 274 participants; very low-certainty evidence) or readmissions (RR not estimable, 95% CI not estimable; I2 = not applicable; 1 study, 50 participants; very low-certainty evidence). We found no studies comparing tubeless mini versus standard mini-PNL or totally tubeless mini versus standard mini-PNL. AUTHORS' CONCLUSIONS: When comparing tubeless to standard PNL with regard to the predefined primary outcomes of this review, there may be little difference in early postoperative pain, while we are very uncertain of the effect on SAEs. People treated with tubeless PNL may benefit from a reduced length of stay compared to standard PNL. When comparing totally tubeless to standard PNL, early postoperative pain and severe adverse events may be reduced with totally tubeless PNL. The certainty of evidence by outcome was mostly very low (range: moderate to very low) for the comparison of tubeless to standard PNL and low (range: moderate to very low) for the comparison of totally tubeless to standard PNL. The most common reasons for downgrading the certainty of the evidence were study limitations, inconsistency, and imprecision. We did not find randomized trial evidence for other comparisons. Overall, further and higher-quality studies are needed to inform clinical practice.

Development of the NOGGO GIS v1 Assay, a Comprehensive Hybrid-Capture-Based NGS Assay for Therapeutic Stratification of Homologous Repair Deficiency Driven Tumors and Clinical Validation.

The worldwide approval of the combination maintenance therapy of olaparib and bevacizumab in advanced high-grade serous ovarian cancer requires complex molecular diagnostic assays that are sufficiently robust for the routine detection of driver mutations in homologous recombination repair (HRR) genes and genomic instability (GI), employing formalin-fixed (FFPE) paraffin-embedded tumor samples without matched normal tissue. We therefore established a DNA-based hybrid capture NGS assay and an associated bioinformatic pipeline that fulfils our institution's specific needs. The assay´s target regions cover the full exonic territory of relevant cancer-related genes and HRR genes and more than 20,000 evenly distributed single nucleotide polymorphism (SNP) loci to allow for the detection of genome-wide allele specific copy number alterations (CNA). To determine GI status, we implemented an %CNA score that is robust across a broad range of tumor cell content (25-85%) often found in routine FFPE samples. The assay was established using high-grade serous ovarian cancer samples for which BRCA1 and BRCA2 mutation status as well as Myriad MyChoice homologous repair deficiency (HRD) status was known. The NOGGO (Northeastern German Society for Gynecologic Oncology) GIS (GI-Score) v1 assay was clinically validated on more than 400 samples of the ENGOT PAOLA-1 clinical trial as part of the European Network for Gynaecological Oncological Trial groups (ENGOT) HRD European Initiative. The "NOGGO GIS v1 assay" performed using highly robust hazard ratios for progression-free survival (PFS) and overall survival (OS), as well a significantly lower dropout rate than the Myriad MyChoice clinical trial assay supporting the clinical utility of the assay. We also provide proof of a modular and scalable routine diagnostic method, that can be flexibly adapted and adjusted to meet future clinical needs, emerging biomarkers, and further tumor entities.

[Stress experience by information and communication technologies among nurses in outpatient care - A qualitative interview study]. / Belastungserleben durch Informations- und Kommunikationstechnologien bei Pflegefachpersonen in der ambulanten Pflege.

Stress experience by information and communication technologies among nurses in outpatient care - A qualitative interview study Abstract: Background: "Work 4.0" is also becoming increasingly prevalent in outpatient care through information and communication technologies (ICT). In addition to a variety of options that ICT offers nursing staff, its use leads to additional stresses. Aims: The aim of the study is to identify relevant stress categories that are caused using ICT and provide an additional influence on the stress experience of employees in outpatient care. Methods: Problem-centred interviews were conducted with eight nurses from three outpatient care organizations as part of a qualitative study. Subsequently, these interviews were transcribed and evaluated using qualitative content analysis according to Mayring. Results: Ten factors were identified that were perceived as stress by ambulatory care employees: for example, insufficient participation and usability, increased documentation effort, information overload. Regarding the employees' ability to work and their health, no relevant impairments could be derived that could be attributed to the identified additional strains. Conclusions: Further analysis of the potential stress situations that could result from ICT use is needed to include this knowledge in primary prevention. It makes sense to establish demand-, participation-, and process-oriented structures in outpatient care organizations. The use of ICT can also be an advantage because, for example, information can be obtained more quickly.

Prevention and Treatment of Social Anxiety Disorder in Adolescents: Protocol for a Randomized Controlled Trial of the Online Guided Self-Help Intervention SOPHIE.

BACKGROUND: Social anxiety symptoms are highly prevalent among adolescents and are associated with poor quality of life and low psychosocial functioning. If untreated, social anxiety often persists into adulthood and increases the risk for comorbid disorders. Therefore, early interventions for social anxiety to prevent negative long-term consequences are critical. However, adolescents rarely seek help and often avoid face-to-face psychotherapeutic interventions due to the perceived lack of autonomy and anonymity. Thus, online interventions represent a promising opportunity to reach adolescents who have social anxiety but do not seek help yet. OBJECTIVE: This study aims to evaluate the efficacy, moderators, and mediators of an online intervention developed to reduce social anxiety in adolescents. METHODS: A total of 222 adolescents aged 11-17 years with subclinical social anxiety (N=166) or with a diagnosis of social anxiety disorder (N=56) are randomly assigned to the online intervention or a care-as-usual control group. The 8-week guided online intervention is based on the Cognitive Model of Social Phobia and evidence-based online interventions for social anxiety adapted to the specific needs of adolescents. The care-as-usual group will be given access to the online intervention after the follow-up assessment. Participants are assessed at baseline, at 4 and 8 weeks post intervention, and at 3-month follow-up assessment on the primary outcome, that is, social anxiety, on secondary outcomes (eg, level of functioning, fear and avoidance, general anxiety, depression, quality of life, self-esteem, and negative effects of the intervention), on potential moderators (eg, therapy motivation, therapy expectancy, and satisfaction with the intervention), and potential mediators (eg, therapeutic alliance and adherence to the intervention). Data will be analyzed based on an intention-to-treat approach and both groups (intervention and care-as-usual) will be compared at each assessment time point. Furthermore, potential mechanisms of change and generalization of intervention effects on daily life are assessed using an ecological momentary assessment procedure that includes items on maintaining mechanisms of social anxiety, social context, and affect. Participants are prompted 3 times a day during the first 8 weeks of the study and again for 2 weeks following the follow-up assessment. RESULTS: Recruitment is ongoing; initial results are expected in 2024. CONCLUSIONS: Results are discussed considering the potential of online interventions as a low-threshold prevention and treatment option for adolescents with social anxiety and in light of current advances in dynamic modeling of change processes and mechanisms in early intervention and psychotherapy in adolescents. TRIAL REGISTRATION: ClinicalTrials.gov NCT04782102; https://clinicaltrials.gov/ct2/show/NCT04782102. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44346.

Mediators of outcome in adolescent psychotherapy and their implications for theories and mechanisms of change: a systematic review.

Psychotherapeutic treatment of adolescents requires age-specific approaches and thus plausibly also involves different change mechanisms than adult psychotherapy. To guide further research and improve therapeutic outcomes for adolescents, we reviewed all RCTs investigating mechanisms of change in the psychological treatment of adolescents to identify the most promising age-, disorder- or treatment-specific mediators. Following the preferred reporting items for systematic reviews (PRISMA), 106 studies were included that reported 252 statistical mediation tests assessed with 181 different measures. Most often studied and significant mediators were cognitive, followed by family-related, and behavioral variables. Several mediators were identified to be promising for future investigations: changes in negative thoughts, dysfunctional beliefs and metacognitive skills; family functioning and parenting skills; as well as successful engagement in therapy activities and increased impulse control. Symptom change during therapy was least often a mediator for other therapeutic changes. Relational and emotional mediators were largely understudied, whereas peer-influence appeared a promising mediator for intervention outcomes. Adolescence-specific mediators were most commonly investigated. Majority of studied mediators were not disorder-specific. There was a tendency to mainly test change mechanisms of specific theoretical models without considering other possible change theories. Further, virtually no studies fulfilled all criteria for rigorously investigating mediation and only nine were classified with an overall good study quality. While bearing in mind the current limitations in study designs, methodological rigor and reporting, there appears to be substantial evidence for transdiagnostic age-specific change models in the psychological treatment of adolescents. For future research, need for consensus on a core set of transdiagnostic and transtheoretical mediators and measures is highlighted. These should address likely core mechanisms of change, as well as take into account age-relevant developmental challenges and biological markers.

Study protocol of an observational study in acute psychiatric home treatment: How does home treatment work? Identification of common factors and predictors of treatment success.

BACKGROUND: Systematic reviews indicated that home treatment is an effective and cost-saving alternative to conventional acute psychiatric treatment options. Treatment success has often been defined as a reduction of hospital admissions. In the current study, symptoms and well-being are assessed regularly during treatment as an indicator for treatment success. Patients' characteristics such as diagnosis, age, substance use, and motivation for treatment were discussed as predictors for treatment success. A second focal point of the study lies in the examination of the therapeutic relationship in terms of the outcome, which has not yet been systematically investigated in home treatment. METHODS: This is an observational study with a prospective naturalistic design. Measurements are carried out at baseline, during and at the end of treatment as well as at the 3­month follow-up. Patients' characteristics as potential predictors for treatment success will be assessed at baseline. In addition, the perceived relationship between the patients and the team will be measured daily and weekly throughout the treatment. Treatment success is by the changes in symptoms and general well-being assessed weekly. We aim to include 82 participants assigned to home treatment. Variance analyses with repeated measurements will be conducted to evaluate treatment success. CONCLUSION: By examining potential patient- and relationship-related predictors of treatment success, insights into relevant determining variables of treatment success in this setting are expected. The results might help to better identify who benefits the most from home treatment.

Response of an HER2-Mutated NSCLC Patient to Trastuzumab Deruxtecan and Monitoring of Plasma ctDNA Levels by Liquid Biopsy.

HER2-targeted therapy is currently the subject of several studies in lung cancer and other solid tumors using either tyrosine kinase inhibitors (TKI) or targeted-antibody-drug conjugates. We describe a 61-year-old female patient with HER2 mutated adenocarcinoma of the lungs who received chemo-immunotherapy, followed by trastuzumab deruxtecan (T-DXd) and third-line Ramucirumab/Docetaxel at disease progression. Plasma ctDNA monitoring was obtained at 12 timepoints during therapy and revealed HER2 mutation allele frequencies that corresponded to the clinical course of disease. HER2-targeted T-DXd therapy resulted in a profound clinical response and may be an option for NSCLC patients carrying an activated HER2 mutation. Longitudinal liquid biopsy quantification of the underlying driver alteration can serve as a powerful diagnostic tool to monitor course of therapy.

Increasing Biomarker Guidance in the Treatment of Urothelial Carcinoma: Systematic Review of International Clinical Trials.

PURPOSE: Precision oncology requires biomarker testing from tumor tissue for clinical decision-making and selection of targeted therapies. We systematically evaluated the role of tissue biomarker testing within interventional clinical trials for locally advanced and metastatic urothelial carcinoma (UC). METHODS: A systematic search within the publicly available ClinicalTrials.gov database was performed for the period 1995 to January 2020. We searched for all interventional studies on systemic treatments for advanced UC. Two investigators independently screened the records and extracted the data for statistical analyses. RESULTS: We included 356 studies out of 827 initial records in the final analysis. The overall number of interventional trials in UC patients significantly increased during the past 25 years. Forty-three studies (12.1%) required specific biomarker testing as a prerequisite for inclusion. Of the remaining 313 trials, explorative biomarkers of interest were studied in 83 studies (23.3%). In trials with obligate biomarker testing as a precondition for study inclusion, only 3 studies (7%) required an actual fresh pretreatment biopsy, while the majority of studies did not state any tissue requirements (55.8%) or accepted archival tissue samples (37.3%). Among studies without biomarker prerequisites, freshly obtained tissue samples were required in 16.3% of studies evaluating immune checkpoint inhibition and 5.7% evaluating targeted therapy. The collection of archival tissue was allowed in 67.4% and 20% of studies evaluating immune checkpoint inhibitors and targeted therapies, respectively. CONCLUSION: There has been an increase in the number of studies using biomarker-guided interventions for the treatment of advanced UC over the past 25 years. Studies investigating druggable targets in actual UC biopsies immediately before treatment are still rare. Standardized criteria for tissue-based biomarker testing may further accelerate personalized treatment of patients with advanced UC.

Salud mental, padecimiento y labor docente / Saúde mental, adoecimento e trabalho docente / Mental health, illness and teaching work

RESUMO A percepção dos docentes de Ensino Fundamental sobre a sua saúde mental foi o foco desta pesquisa. Trata-se de uma pesquisa quantitativa que procura compreender as percepções das condições de saúde mental de escolas públicas no interior do Rio Grande do Sul, Brasil. O método da coleta de dados utilizado foi um questionário adaptado do Protocolo de Atenção à Saúde Mental e Trabalho respondido por 249 professores. Realizou-se a análise dos dados por intermédio do software Statistical Package for the Social Sciences - SPSS 18. Encontrou-se, como principais resultados, que índices de satisfação, motivação e identidade com a atividade docente são muito significativos. Os professores indicam comprometimento com o trabalho, valorizam a profissão, mas queixam-se de que socialmente não são valorizados, mas paradoxalmente estão muito medicados.

RESUMEN La percepción de los docentes de educación básica sobre su salud mental fue el enfoque de esta investigación. El objetivo de esta investigación cuantitativa fue comprender de esas percepciones las condiciones de salud mental de escuelas públicas en el interior de RS, Brasil. El método de la recolecta de datos utilizado fue un cuestionario adaptado del Protocolo de Atención a la Salud Mental y Labor respondido por 249 profesores. Se realizó el análisis de los datos por intermedio del software Statistical Package for the Social Sciences - SPSS 18. Se encontró, como principales resultados, que índices de satisfacción, motivación e identidad con la actividad docente son muy significativos. Los profesores indican comprometimiento con el trabajo, valoran la profesión, pero se quejan de que socialmente no son valorizados, sin embargo, paradoxalmente están muy medicados.

ABSTRACT The perception of Elementary School teachers about their mental health was the focus of this research. This is a quantitative research that seeks to understand the perceptions of mental health conditions in public schools in the interior of Rio Grande do Sul, Brazil. The data collection method used was a questionnaire adapted from the Mental Health and Work Protocol answered by 249 teachers. Data analysis was carried out using the Statistical Package for the Social Sciences - SPSS 18 software. It was found, as main results, that satisfaction, motivation and identity indices with the teaching activity are very significant. Teachers indicate commitment to work, value the profession, but complain that socially they are not valued, but paradoxically are heavily medicated.

"Desgastes e sacrifícios" medicados: a relação trabalho e adoecimento na vida das professoras brasileiras / "Wear and sacrifices" medicated: The relationship between work and illness in the Brazilian teachers life's / "Desgaste y sacrificios" medicados: La relación entre el trabajo y la enfermedad en la vida de los maestros brasileños

O trabalho docente e suas condições de produção geram agravos à saúde. Uma grande parcela dos docentes tem apresentado riscos de adoecimento e transtornos psíquicos. Assim, este estudo objetivou identificar e analisar, de forma estatística e sob a perspectiva da Análise de Conteúdo, respostas frente a depoimentos de docentes formulados sobre os cuidados dispensados à saúde. Foi verificada, por meio dessas respostas, a relação das docentes com a medicação e, a partir disso, foi estabelecido como são utilizados os medicamentos psicofarmacológicos pelas professoras de ensino básico. Participaram 89 profissionais, que responderam um questionário on-line, os resultados demonstraram que a medicação é um recurso preocupante, 54% participantes utilizam medicação frente ao adoecimento relativo ao trabalho docente; relatam estresse e violência no contexto escolar, sendo vivenciados cotidianamente. Conclui-se, assim, que estão medicados e precisam de espaços de escuta e políticas públicas frente ao agravamento das condições de saúde

The teaching work and its production conditions generate health problems. A large proportion of teachers have presented risks of illness and psychic disorders. Thus, this study aimed to identify and analyze statistically and from the perspective of Content Analysis, answers to statements of teachers formulated about health care. Through these answers, we verified the relationship of teachers with medication and, from this, it was established how psychopharmacological drugs are used by primary school teachers. Participants were 89 professionals who answered an online questionnaire, the results showed that medication is a worrying resource, 54% of the participants use medication in the face of illness related to teaching work; report stress and violence in the school context, being experienced daily. Thus, it is concluded that they are medicated and need listening spaces and public policies in the face of worsening health conditions

El trabajo docente y sus condiciones de producción generan problemas de salud. Una gran proporción de maestros han presentado riesgos de enfermedad y trastornos psíquicos. Así, este estudio tuvo como objetivo identificar y analizar estadísticamente y desde la perspectiva del Análisis de Contenido, las respuestas a las declaraciones de las docentes formuladas sobre el cuidado de la salud. Fué verificado, a través de estas respuestas, la relación de los docentes con la medicación y, a partir de esto, fué establecido cómo son utilizados los medicamentos psicofarmacológicos. Los participantes fueron 89 profesionales que respondieron a un cuestionario en línea, los resultados demuestran que la medicación es un recurso preocupante, el 54% de los participantes utilizan medicación frente a enfermedades relacionadas con la labor docente; reportan estrés y violencia en el contexto escolar, siendo experimentado diariamente. Así, se concluye que están medicados y necesitan espacios de escucha y políticas públicas ante el empeoramiento de las condiciones de salud

Quantification of Remimazolam Besylate (CNS7056B) and Its Metabolite (CNS7054X) by LC-MS/MS in Human Plasma Using Midazolam-d4 Maleate as Internal Standard.

A new assay was developed to measure the concentration of remimazolam besylate (CNS7056B) and its major carboxylic acid metabolite (CNS7054X) in human plasma. For this new assay method, midazolam-d4 maleate was used as an internal standard. After setting up a previously described assay method, using CNS7056-d4 and CNS7054-d4 as internal standards, analytical results of both methods were compared. For the new analytical method, ultra-high-performance liquid chromatography (UHPLC) with tandem mass spectrometry was applied. A purification method, using solid phase extraction, was developed and validated. The chromatographic separation of the analytes was achieved with a mobile phase gradient using a Water Acquity™ UHPLC-System. The Kinetex™ biphenyl 50 × 2.1 mm UHPLC column was used with a particle diameter of 1.7 µm (Phenomenex, Germany). A measuring range of 0.6-2,000 ng/mL for CNS7056B and of 6-20,000 ng/mL for CNS7054X could be achieved with this new assay. The lower limit of quantification was 0.6 ng/mL for CNS7056B and 6 ng/mL for CNS7054X. The assay was validated according to US Food and Drug Administration guidelines. The new method showed an accuracy of 96.9-110.4% and a precision of 2.1-6.7% for both analytes.

Mediators of quality of life change in people with severe psychotic disorders treated in integrated care: ACCESS II study.

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, ß = -0.20, p < 0.001) to QoL (12 months, ß = -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 (ß = 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.

Testicular germ cell tumours' clinical stage I: comparison of surveillance with adjuvant treatment strategies regarding recurrence rates and overall survival-a systematic review.

PURPOSE: Testicular germ cell tumours (GCTs) represent the most common malignancy in young adult males with two thirds of all cases presenting with clinical stage I (CSI). Active surveillance is the management modality mostly favoured by current guidelines. This systematic review assesses the treatment results in CSI patients concerning recurrence rate and overall survival in non-seminoma (NS) and pure seminoma (SE) resulting from surveillance in comparison to adjuvant strategies. METHODS/SYSTEMATIC REVIEW: We performed a systematic literature review confining the search to most recent studies published 2010-2021 that reported direct comparisons of surveillance to adjuvant management. We searched Medline and the Cochrane Library with additional hand-searching of reference lists to identify relevant studies. Data extraction and quality assessment of included studies were performed with stratification for histology (NS vs. SE) and treatment modalities. The results were tabulated and evaluated with descriptive statistical methods. RESULTS: Thirty-four studies met the inclusion criteria. In NS patients relapse rates were 12 to 37%, 0 to 10%, and 0 to 11.8% for surveillance, chemotherapy and for retroperitoneal lymph node dissection (RPLND) while overall survival rates were 90.7-100%, 91.7-100%, and 97-99.1%, respectively. In SE CSI, relapse rates were 0-22.3%, 0-5%, and 0-12.5% for surveillance, radiotherapy, chemotherapy, while overall survival rates were 84.1-98.7%, 83.5-100%, and 92.3-100%, respectively. CONCLUSION: In both histologic subgroups, active surveillance offers almost identical overall survival as adjuvant management strategies, however, at the expense of higher relapse rates. Each of the management strategies in CSI GCT patients have specific merits and shared-decision-making is advised to tailor treatment.