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.

Who Benefits from Acute Psychiatric Home Treatment? A Systematic Review.

Home treatment (HT) treats patients in an acute crisis through an interdisciplinary team with daily appointments for a short treatment period. The effectiveness of HT has already been confirmed. However, only few studies addressed specific patient characteristics associated outcome of treatment. This study aimed to identify patient characteristics associated with successful outcomes of HT. A systematic literature search was conducted according to the PRISMA guidelines. A total of 13 studies were included in the systematic review. Being employed, having a regular income, having an anxiety disorder and family involvement were associated with a successful treatment outcome in HT. High symptom severity and former hospital admissions were associated with unsuccessful treatment outcome in HT in the selected studies. HT seems to be especially beneficial for patients with paid employment or regular income, patients with anxiety disorders, and patients with familial or other social support.

Child maltreatment and hypothalamic-pituitary-adrenal axis functioning: A systematic review and meta-analysis.

Alterations in hypothalamic-pituitary-adrenal (HPA) axis and its effector hormone cortisol have been proposed as one possible mechanism linking child maltreatment experiences to health disparities. In this series of meta-analyses, we aimed to quantify the existing evidence on the effect of child maltreatment on various measures of HPA axis activity. The systematic literature search yielded 1,858 records, of which 87 studies (k = 132) were included. Using random-effects models, we found evidence for blunted cortisol stress reactivity in individuals exposed to child maltreatment. In contrast, no overall differences were found in any of the other HPA axis activity measures (including measures of daily activity, cortisol assessed in the context of pharmacological challenges and cumulative measures of cortisol secretion). The impact of several moderators (e.g., sex, psychopathology, study quality), the role of methodological shortcomings of existing studies, as well as potential directions for future research are discussed.

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.

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.

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.

[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.

How to classify, diagnose, treat and follow-up extragonadal germ cell tumors? A systematic review of available evidence.

PURPOSE: To present the current evidence and the development of studies in recent years on the management of extragonadal germ cell tumors (EGCT). METHODS: A systematic literature search was conducted in Medline and the Cochrane Library. Studies within the search period (January 2010 to February 2021) that addressed the classification, diagnosis, prognosis, treatment, and follow-up of extragonadal tumors were included. Risk of bias was assessed and relevant data were extracted in evidence tables. RESULTS: The systematic search identified nine studies. Germ cell tumors (GCT) arise predominantly from within the testis, but about 5% of the tumors are primarily located extragonadal. EGCT are localized primarily mediastinal or retroperitoneal in the midline of the body. EGCT patients are classified according to the IGCCCG classification. Consecutively, all mediastinal non-seminomatous EGCT patients belong to the "poor prognosis" group. In contrast mediastinal seminoma and both retroperitoneal seminoma and non-seminoma patients seem to have a similar prognosis as patients with gonadal GCTs and metastasis at theses respective sites. The standard chemotherapy regimen for patients with a EGCT consists of 3-4 cycles (good vs intermediate prognosis) of bleomycin, etoposid, cisplatin (BEP); however, due to their very poor prognosis patients with non-seminomatous mediastinal GCT should receive a dose-intensified or high-dose chemotherapy approach upfront on an individual basis and should thus be referred to expert centers Ifosfamide may be exchanged for bleomycin in cases of additional pulmonary metastasis due to subsequently planned resections. In general patients with non-seminomatous EGCT, residual tumor resection (RTR) should be performed after chemotherapy. CONCLUSION: In general, non-seminomatous EGCT have a poorer prognosis compared to testicular GCT, while seminomatous EGGCT seem to have a similar prognosis to patients with metastatic testicular seminoma. The current insights on EGCT are limited, since all data are mainly based on case series and studies with small patient numbers and non-comparative studies. In general, systemic treatment should be performed like in testicular metastatic GCTs but upfront dose intensification of chemotherapy should be considered for mediastinal non-seminoma patients. Thus, EGCT should be referred to interdisciplinary centers with utmost experience in the treatment of germ cell tumors.

Can magnetic resonance imaging replace conventional computerized tomography for follow-up of patients with testicular cancer? A systematic review.

PURPOSE: Follow-up protocols for patients with testicular cancer (TC) have significantly reduced the number of cross-sectional imaging studies to reduce radiation exposure. At present, it is unclear whether magnetic resonance imaging (MRI) could replace conventional computerized tomography (CT) imaging. The objective of this study is to summarize the scientific evidence on this topic and to review guideline recommendations with regard to the use of MRI. METHODS: A systematic literature review was performed searching Medline and Cochrane databases for prospective studies on patients with TC in the follow-up care (last search in February 2021). Additionally, guideline recommendations for TC were screened. Data extraction and quality assessment of included studies were performed and used for a descriptive presentation of results. RESULTS: A total of four studies including two ongoing trials were identified. Overall, the scientific evidence of prospective comparative studies is based on 102 patients. Data suggest that abdominal imaging with MRI can replace conventional CT for detection of lymph node metastasis of the retroperitoneum to spare radiation exposure and contrast media application. However, experienced radiologists are needed. Clinical guidelines are aware of the risk of diagnosis-induced secondary malignancy due to CT imaging and some have adapted their recommendations accordingly. Results of the two ongoing trials on 738 patients are expected soon to provide more reliable results on this topic. CONCLUSIONS: There is growing evidence that abdominopelvic MRI imaging can replace CT imaging during follow-up of patients with TC in order to reduce radiation exposure and diagnosis-induced secondary malignancy.

Prognostic factors in patients with clinical stage I nonseminoma-beyond lymphovascular invasion: a systematic review.

OBJECTIVE: To systematically evaluate evidence on prognostic factors for tumor recurrence in clinical stage I nonseminoma patients other than lymphovascular invasion (LVI). METHODS: We performed a systematic literature search in the biomedical databases Medline (via Ovid) and Cochrane Central Register of Controlled Trials (search period January 2010 to February 2021) for full text publications in English and German language, reporting on retro- or prospectively assessed prognostic factors for tumor recurrence in patients with stage I nonseminomatous germ cell tumors. RESULTS: Our literature search yielded eleven studies reporting on 20 potential prognostic factors. Results are based on cohort studies of mostly moderate to low quality. Five out of eight studies found a significant association of embryonal carcinoma (EC) in the primary tumor with relapse. Among the different risk definitions of embryonal carcinoma (presence, predominance, pure), presence of EC alone seems to be sufficient for prognostification. Interesting results were found for rete testis invasion, predominant yolk sac tumor, T-stage and history of cryptorchidism, but the sparse data situation does not justify their clinical use. CONCLUSIONS: No additional factors that meet the prognostic value of LVI, especially when determined by immunohistochemistry, could be identified through our systematic search. The presence of EC might serve as a second, subordinate prognostic factor for clinical use as the data situation is less abundant than the one of LVI. Further efforts are necessary to optimize the use of these two prognostic factors and to evaluate and validate further potential factors with promising preliminary data.

First-line salvage treatment options for germ cell tumor patients failing stage-adapted primary treatment : A comprehensive review compiled by the German Testicular Cancer Study Group.

PURPOSE: In this review, we summarize and discuss contemporary treatment standards and possible selection criteria for decision making after failure of adjuvant or first-line cisplatin-based chemotherapy for primarily localized or metastatic germ cell tumors. METHODS: This work is based on a systematic literature search conducted for the elaboration of the first German clinical practice guideline to identify prospective clinical trials and retrospective comparative studies published between Jan 2010 and Feb 2021. Study end points of interest were progression-free (PFS) and overall survival (OS), relapse rate (RR), and/or safety. RESULTS: Relapses of clinical stage I (CS I) patients irrespective of prior adjuvant treatment after orchiectomy are treated stage adapted in accordance for primary metastatic patients. Surgical approaches for sole retroperitoneal relapses are investigated in ongoing clinical trials. The appropriate salvage chemotherapy for metastatic patients progressing or relapsing after first-line cisplatin-based chemotherapy is still a matter of controversy. Conventional cisplatin-based chemotherapy is the international guideline-endorsed standard of care, but based on retrospective data high-dose chemotherapy and subsequent autologous stem cell transplantation may offer a 10-15% survival benefit for all patients. Secondary complete surgical resection of all visible residual masses irrespective of size is paramount for treatment success. CONCLUSIONS: Patients relapsing after definite treatment of locoregional disease are to be treated by stage-adapted first-line standard therapy for metastatic disease. Patients with primary advanced/metastatic disease failing one line of cisplatin-based combination chemotherapy should be referred to GCT expert centers. Dose intensity is a matter of ongoing debate, but sequential high-dose chemotherapy seems to improve patients' survival.

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.

Therapy of clinical stage IIA and IIB seminoma: a systematic review.

PURPOSE: The optimal treatment for clinical stage (CS) IIA/IIB seminomas is still controversial. We evaluated current treatment options. METHODS: A systematic review was performed. Only randomized clinical trials and comparative studies published from January 2010 until February 2021 were included. Search items included: seminoma, CS IIA, CS IIB and therapy. Outcome parameters were relapse rate (RR), relapse-free (RFS), overall and cancer-specific survival (OS, CSS). Additionally, acute and long-term side effects including secondary malignancies (SMs) were analyzed. RESULTS: Seven comparative studies (one prospective and six retrospective) were identified with a total of 5049 patients (CS IIA: 2840, CS IIB: 2209). The applied treatment modalities were radiotherapy (RT) (n = 3049; CS IIA: 1888, CSIIB: 1006, unknown: 155) and chemotherapy (CT) or no RT (n = 2000; CS IIA: 797, CS IIB: 1074, unknown: 129). In CS IIA, RRs ranged from 0% to 4.8% for RT and 0% for CT. Concerning CS IIB RRs of 9.5%-21.1% for RT and of 0%-14.2% for CT have been reported. 5-year OS ranged from 90 to 100%. Only two studies reported on treatment-related toxicities. CONCLUSIONS: RT and CT are the most commonly applied treatments in CS IIA/B seminoma. In CS IIA seminomas, RRs after RT and CT are similar. However, in CS IIB, CT seems to be more effective. Survival rates of CS IIA/B seminomas are excellent. Consequently, long-term toxicities and SMs are important survivorship issues. Alternative treatment approaches, e.g., retroperitoneal lymph node dissection (RPLND) or dose-reduced sequential CT/RT are currently under prospective investigation.

Guideline-Based Quality Indicators for Kidney and Bladder Cancer in Germany: Development and Implementation.

INTRODUCTION: As part of the development of the evidence-based (S3) clinical practice guidelines for kidney and bladder cancer by the German Guideline Program in Oncology, quality indicators (QIs) were defined to measure the quality of care. Based on these guidelines and QIs, the German Cancer Society (DKG) developed two new certification systems. The aim of this article is to show the process of development and implementation of QIs in certified cancer centres. METHODS: Based on strong recommendations of each guideline and an additional systematic literature review for national and international QIs, two sets of QIs were derived in a multistep standardized approach. These QIs were implemented in the centres in certification data sheets to measure their outcomes. First results of treatment years 2018 and 2019 are available. RESULTS: The final sets include 9 QIs for kidney cancer and 12 QIs for bladder cancer. Two-thirds of the QIs were transferred to the data sheets. In 2018 and 2019, the results of all but one QI are within the plausibility limits. From 2020 on, they are replaced by stricter target values that will challenge centres to improve their outcomes. CONCLUSIONS: Guideline-derived QIs make relevant aspects of patient care measurable and consequently improvable. The first QI results are encouraging. However, the DKG certification system and the methods of measuring quality are under ongoing development. Systematic QI implementation and evaluation may help to generate broader databases and thus expand knowledge.

Introducing a Group Therapy Program (PLAN D) for Young Outpatients with Derealization and Depersonalization: A Pilot Study.

Depersonalization and derealization (DD) cause significant distress and are associated with poor role and social functional outcomes. Despite the relatively high prevalence of DD symptoms and the chronic course in those suffering from a DD disorder, there still exists a need for effective interventions. Preliminary evidence indicates that cognitive behavioral therapy (CBT) delivered in an individual setting demonstrates some positive intervention effects for patients with DD regarding their symptom levels. By considering DD-specific treatment needs, a group therapy program was developed as an add-on therapy based on CBT techniques called PLAN D comprising the following elements: psychoeducation, lifestyle interventions, acceptance and mindfulness training, and new patterns of DD-related cognitions. In a pilot study, we present an 8-week group intervention for adolescents and young adults with DD disorder. To our knowledge, no standardized group intervention program for DD exists so far. Thus, this novel intervention represents a promising opportunity to positively influence long-term outcomes and course of DD.

The domestic pig as human-relevant large animal model to study adaptive antifungal immune responses against airborne Aspergillus fumigatus.

Pulmonary mucosal immune response is critical for preventing opportunistic Aspergillus fumigatus infections. Although fungus-specific CD4+ T cells in blood are described to reflect the actual host-pathogen interaction status, little is known about Aspergillus-specific pulmonary T-cell responses. Here, we exploit the domestic pig as human-relevant large animal model and introduce antigen-specific T-cell enrichment in pigs to address Aspergillus-specific T cells in the lung compared to peripheral blood. In healthy, environmentally Aspergillus-exposed pigs, the fungus-specific T cells are detectable in blood in similar frequencies as observed in healthy humans and exhibit a Th1 phenotype. Exposing pigs to 106 cfu/m3 conidia induces a long-lasting accumulation of Aspergillus-specific Th1 cells locally in the lung and also systemically. Temporary immunosuppression during Aspergillus-exposure showed a drastic reduction in the lung-infiltrating antifungal T-cell responses more than 2 weeks after abrogation of the suppressive treatment. This was reflected in blood, but to a much lesser extent. In conclusion, by using the human-relevant large animal model the pig, this study highlights that the blood clearly reflects the mucosal fungal-specific T-cell reactivity in environmentally exposed as well as experimentally exposed healthy pigs. But, immunosuppression significantly impacts the mucosal site in contrast to the initial systemic immune response.

Degarelix for treating advanced hormone-sensitive prostate cancer.

BACKGROUND: Degarelix is a gonadotropin-releasing hormone antagonist that leads to medical castration used to treat men with advanced or metastatic prostate cancer, or both. It is unclear how its effects compare to standard androgen suppression therapy. OBJECTIVES: To assess the effects of degree compared with standard androgen suppression therapy for men with advanced hormone-sensitive prostate cancer. SEARCH METHODS: We searched multiple databases (CENTRAL, MEDLINE, Embase, Scopus, Web of Science, LILACS until September 2020), trial registries (until October 2020), and conference proceedings (until December 2020). We identified other potentially eligible trials by reference checking, citation searching, and contacting study authors. SELECTION CRITERIA: We included randomized controlled trials comparing degarelix with standard androgen suppression therapy for men with advanced prostate cancer. DATA COLLECTION AND ANALYSIS: Three review authors independently classified studies and abstracted data from the included studies. The primary outcomes were overall survival and serious adverse events. Secondary outcomes were quality of life, cancer-specific survival, clinical progression, other adverse events, and biochemical progression. We used a random-effects model for meta-analyses and assessed the certainty of evidence for the main outcomes according to GRADE. MAIN RESULTS: We included 11 studies with a follow-up of between three and 14 months. We also identified five ongoing trials. Primary outcomes Data to evaluate overall survival were not available.  Degarelix may result in little to no difference in serious adverse events compared to standard androgen suppression therapy (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.62 to 1.05; low-certainty evidence; 2750 participants). Based on 114 serious adverse events in the standard androgen suppression group, this corresponds to 23 fewer serious adverse events per 1000 participants (43 fewer to 6 more). We downgraded the certainty of evidence for study limitations and imprecision. Secondary outcomes Degarelix likely results in little to no difference in quality of life assessed with a variety of validated questionnaires (standardized mean difference 0.06 higher, 95% CI 0.05 lower to 0.18 higher; moderate-certainty evidence; 2887 participants), with higher scores reflecting better quality of life. We downgraded the certainty of evidence for study limitations. Data to evaluate cancer-specific survival were not available. The effects of degarelix on cardiovascular events are very uncertain (RR 0.15, 95% CI 0.04 to 0.61; very low-certainty evidence; 80 participants). We downgraded the certainty of evidence for study limitations, imprecision, and indirectness as this trial was conducted in a unique group of high-risk participants with pre-existing cardiovascular morbidities. Degarelix likely results in an increase in injection site pain (RR 15.68, 95% CI 7.41 to 33.17; moderate-certainty evidence; 2670 participants). Based on 30 participants per 1000 with injection site pain with standard androgen suppression therapy, this corresponds to 440 more injection site pains per 1000 participants (192 more to 965 more). We downgraded the certainty of evidence for study limitations. We did not identify any relevant subgroup differences for different degarelix maintenance doses. AUTHORS' CONCLUSIONS: We did not find trial evidence for overall survival or cancer-specific survival comparing degarelix to standard androgen suppression, but serious adverse events and quality of life may be similar between groups. The effects of degarelix on cardiovascular events are very uncertain as the only eligible study had limitations, was small with few events, and was conducted in a high-risk population. Degarelix likely results in an increase in injection site pain compared to standard androgen suppression therapy. Maximum follow-up of included studies was 14 months, which is short. There is a need for methodologically better designed and executed studies with long-term follow-up evaluating men with metastatic prostate cancer.

Management of Germ Cell Tumours of the Testes in Adult Patients: German Clinical Practice Guideline, PART II - Recommendations for the Treatment of Advanced, Recurrent, and Refractory Disease and Extragonadal and Sex Cord/Stromal Tumours and for the Management of Follow-Up, Toxicity, Quality of Life, Palliative Care, and Supportive Therapy.

OBJECTIVES: We developed the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up of germ cell tumours (GCT) of the testes in adult patients. We present the guideline content in 2 separate publications. The present second part summarizes therecommendations for the treatment of advanced disease stages and for the management of follow-up and late effects. MATERIALS AND METHODS: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search in March 2018), were provided. Thirty-one experts, who were entitled to vote, rated the final clinical recommendations and statements. RESULTS: Here we present the treatment recommendations separately for patients with metastatic seminoma and non-seminomatous GCT (stages IIA/B and IIC/III), for restaging and treatment of residual masses, and for relapsed and refractory disease stages. The recommendations also cover extragonadal and sex cord/stromal tumours, the management of follow-up and toxicity, quality-of-life aspects, palliative care, and supportive therapy. CONCLUSION: Physicians and other medical service providers who are involved in the diagnostics, treatment, and follow-up of GCT (all stages, outpatient and inpatient care as well as rehabilitation) are the users of the present guideline. The guideline also comprises quality indicators for measuring the implementation of the guideline recommendations in routine clinical care; these data will be presented in a future publication.

Management of Germ Cell Tumours of the Testis in Adult Patients. German Clinical Practice Guideline Part I: Epidemiology, Classification, Diagnosis, Prognosis, Fertility Preservation, and Treatment Recommendations for Localized Stages.

INTRODUCTION: This is the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up on germ cell tumours (GCTs) of the testis in adult patients. We present the guideline content in two publications. Part I covers the topic's background, methods, epidemiology, classification systems, diagnostics, prognosis, and treatment recommendations for the localized stages. METHODS: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search was in March 2018) were provided. Thirty-one experts entitled to vote, rated the final clinical recommendations and statements. RESULTS: We provide 161 clinical recommendations and statements. We present information on the quality of cancer care and epidemiology and give recommendations for staging and classification as well as for diagnostic procedures. The diagnostic recommendations encompass measures for assessing the primary tumour as well as procedures for the detection of metastases. One chapter addresses prognostic factors. In part I, we separately present the treatment recommendations for germ cell neoplasia in situ, and the organ-confined stages (clinical stage I) of both seminoma and nonseminoma. CONCLUSION: Although GCT is a rare tumour entity with excellent survival rates for the localized stages, its management requires an interdisciplinary approach, including several clinical experts. Quality of care is highly related to institutional expertise and can be reassured by established online-based second-opinion boards. There are very few studies on diagnostics with good level of evidence. Treatment of metastatic GCTs must be tailored to the risk according to the International Germ Cell Cancer Collaboration Group classification after careful diagnostic evaluation. An interdisciplinary approach as well as the referral of selected patients to centres with proven experience can help achieve favourable clinical outcomes.

Prognostic models for predicting overall survival in metastatic castration-resistant prostate cancer: a systematic review.

PURPOSE: Prognostic models are developed to estimate the probability of the occurrence of future outcomes incorporating multiple variables. We aimed to identify and summarize existing multivariable prognostic models developed for predicting overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: The protocol was prospectively registered (CRD42017064448). We systematically searched Medline and reference lists up to May 2018 and included experimental and observational studies, which developed and/or internally validated prognostic models for mCRPC patients and were further externally validated or updated. The outcome of interest was overall survival. Two authors independently performed literature screening and quality assessment. RESULTS: We included 12 studies that developed models including 8750 patients aged 42-95 years. Models included 4-11 predictor variables, mostly hemoglobin, baseline PSA, alkaline phosphatase, performance status, and lactate dehydrogenase. Very few incorporated Gleason score. Two models included predictors related to docetaxel and mitoxantrone treatments. Model performance after internal validation showed similar discrimination power ranging from 0.62 to 0.73. Overall survival models were mainly constructed as nomograms or risk groups/score. Two models obtained an overall judgment of low risk of bias. CONCLUSIONS: Most models were not suitable for clinical use due to methodological shortcomings and lack of external validation. Further external validation and/or model updating is required to increase prognostic accuracy and clinical applicability prior to their incorporation in clinical practice as a useful tool in patient management.