Small-molecule inhibitors of human mitochondrial DNA transcription.

Altered expression of mitochondrial DNA (mtDNA) occurs in ageing and a range of human pathologies (for example, inborn errors of metabolism, neurodegeneration and cancer). Here we describe first-in-class specific inhibitors of mitochondrial transcription (IMTs) that target the human mitochondrial RNA polymerase (POLRMT), which is essential for biogenesis of the oxidative phosphorylation (OXPHOS) system1-6. The IMTs efficiently impair mtDNA transcription in a reconstituted recombinant system and cause a dose-dependent inhibition of mtDNA expression and OXPHOS in cell lines. To verify the cellular target, we performed exome sequencing of mutagenized cells and identified a cluster of amino acid substitutions in POLRMT that cause resistance to IMTs. We obtained a cryo-electron microscopy (cryo-EM) structure of POLRMT bound to an IMT, which further defined the allosteric binding site near the active centre cleft of POLRMT. The growth of cancer cells and the persistence of therapy-resistant cancer stem cells has previously been reported to depend on OXPHOS7-17, and we therefore investigated whether IMTs have anti-tumour effects. Four weeks of oral treatment with an IMT is well-tolerated in mice and does not cause OXPHOS dysfunction or toxicity in normal tissues, despite inducing a strong anti-tumour response in xenografts of human cancer cells. In summary, IMTs provide a potent and specific chemical biology tool to study the role of mtDNA expression in physiology and disease.

Prevalence of mental disorders in patients with cancer compared to matched controls - secondary analysis of two nationally representative surveys.

AIM: To compare prevalence rates of mental disorders in patients with cancer and general population controls. METHOD: In two stratified nationally representative surveys, the 12-month prevalence of mental disorders was assessed in 2141 patients with cancer and 4883 general population controls by the standardized Composite International Diagnostic Interview (CIDI). We determined odds ratios (ORs) to compare the odds for mental disorders (combined and subtypes) in cancer patients with age- and gender-matched controls. RESULTS: The 12-month prevalences rate for any mental disorder was significantly higher in patients with cancer compared to controls (OR 1.28, 95% CI 1.14-1.45). Prevalence rates were at least two times higher for unipolar mood disorders (major depression: OR 2.07, 95% CI 1.71-2.51; dysthymia: OR 2.93, 95% CI 2.13-4.02) and mental disorders due to a general medical condition (OR 3.31, 95% CI 2.32-4.71). There was no significant elevation for anxiety disorders overall (OR 0.95, 95% CI 0.81-1.11). Mildly elevated prevalence rates emerged for post-traumatic stress disorder (OR 1.57, 95% CI 1.11-2.23) and social phobia (OR 1.57, 95% CI 1.07-2.31), while specific phobia (OR 0.82, 95% CI 0.67-1.00) and agoraphobia (OR 0.49, 95% CI 0.33-0.73) were significantly less frequent in cancer. CONCLUSIONS: While elevated depression rates reinforce the need for its systematic diagnosis and treatment, lower prevalences were unexpected given previous evidence. Whether realistic illness-related fears and worries contribute to lower occurrence of anxiety disorders with excessive fears in cancer may be of interest to future research.

Thoughts of death and suicidality among patients with cancer: Examining subtypes and their association with mental disorders.

OBJECTIVE: Cancer is associated with an increased risk for completed suicide. We explored subtypes of thoughts of death, death wishes, suicidal ideation and behavior and their association with mental disorders and demographic and disease-related characteristics. METHODS: We studied 2,141 cancer patients with the standardized Composite International Diagnostic Interview-Oncology (CIDI-O). Assessment included 4-weeks-prevalences of thoughts of death, wish to die, suicidal ideation, suicide plans, and lifetime suicide attempts. We further assessed 4-weeks-prevalences of mood, anxiety, adjustment, somatoform, substance use, and disorders due to general medical condition. We conducted latent class analyses (LCA). RESULTS: The LCA identified three classes with distinct patterns of suicidality. Class 1 (89.0% of the sample) showed no suicidality. Class 2 (6.9%) was characterized by thoughts of death without suicidal ideation. Class 3 (4.1%) was characterized by thoughts of death, suicidal ideation, and suicide plans. Death wishes occurred in both classes 2 and 3. Classes 2 and 3 were associated with a significantly higher risk for any mental disorder (OR from 4.22, adjustment disorder, to 10.20, mood disorders, p < 0.001) compared to class 1. Patients with mental disorders were equally likely in classes 2 and 3. Patients with incurable cancer were significantly more likely in class 2, and less likely in class 3. CONCLUSIONS: Cancer patients with suicidal ideation are not distinctly characterized by mental disorders. Further study of concepts that consider problematic adjustment to the cancer stressor such as death anxiety and demoralization may contribute to understand psychological distress underlying subtypes of thoughts of death and suicidality in cancer.

Development and preliminary psychometric investigation of the German Satisfaction with Comprehensive Cancer Care (SCCC) Questionnaire.

PURPOSE: The assessment of patient satisfaction during treatment is essential to provide patient-centered high-quality cancer care. Nevertheless, no German instrument assesses patient satisfaction with comprehensive cancer care, which not only includes oncological treatment, but also interpersonal quality of care as well as psychosocial support services. Based on the French REPERES-60, we developed the German Patient Satisfaction with Comprehensive Cancer Care (SCCC) questionnaire. METHODS: The REPERES-60 was translated and the items were adapted to make it applicable to the German healthcare system and across different tumor entities. Scales of the resulting instrument were extracted via principal axis factoring (PAF). Subsequently, we investigated the reliability (Cronbach's Alpha, CA), discriminatory power (corrected item-scale correlations) and convergent validity (pre-specified correlations of the SCCC with different outcomes). RESULTS: The SCCC consisted of 32 items which were subsequently tested among a sample of 333 patients across different tumor entities (response rate: 47%). Average age was 59 years (standard deviation: 14), 63% were male. PAF revealed four multi-item scales named Competence, Information, Access and Support accounting for 71% of the variance. Two single-items scales assess global satisfaction with medical and psychosocial care, respectively. CA across the multi-item scales ranged from .84 to .96. Discriminatory power was sufficiently high, with all r ≥ .5. Convergent validity was largely verified by negative associations of the four multi-item scales with depressive/anxious symptomatology (r ≥ - .18, p < .01) and fatigue/overall symptom burden (r ≥ - .14, p < .01). CONCLUSION: We developed a tool to assess patient satisfaction with comprehensive cancer care in Germany. The SCCC showed satisfactory psychometric properties. Further studies are needed to verify these preliminary findings.

Risk and associated factors of depression and anxiety in men with prostate cancer: Results from a German multicenter study.

OBJECTIVE: In order to optimize psycho-oncological care, studies that quantify the extent of distress and identify certain risk groups are needed. Among patients with prostate cancer (PCa), findings on depression and anxiety are limited. METHODS: We analyzed data of PCa patients selected from a German multi-center study. Depression and anxiety were assessed with the PHQ-9 and the GAD-7 (cut-off ≥7). We provided physical symptom burden, calculated absolute and relative risk (AR and RR) of depression and anxiety across patient subsets and between patients and the general population (GP) and tested age as a moderator within the relationship of disease-specific symptoms with depression and anxiety. RESULTS: Among 636 participants, the majority reported disease-specific problems (sexuality: 60%; urination: 52%). AR for depression and anxiety was 23% and 22%, respectively. Significant RR were small, with higher risks of distress in patients who are younger (eg, RRdepression = 1.15; 95%-CI: 1.06-1.26), treated with chemotherapy (RRdepression = 1.46; 95%-CI: 1.09-1.96) or having metastases (RRdepression = 1.30; 95%-CI: 1.02-1.65). Risk of distress was slightly elevated compared to GP (eg, RRdepression = 1.13; 95%-CI: 1.07-1.19). Age moderated the relationship between symptoms and anxiety (Burination = -0.10, P = .02; Bsexuality = -0.11, P = .01). CONCLUSIONS: Younger patients, those with metastases or treatment with chemotherapy seem to be at elevated risk for distress and should be closely monitored. Many patients suffer from disease-specific symptom burden, by which younger patients seem to be particularly distressed. Support of coping mechanisms associated with disease-specific symptom burden seems warranted.

Cancer patients' preferred and perceived level of involvement in treatment decision-making: an epidemiological study.

Background: We aimed to analyze preferred and perceived levels of patients' involvement in treatment decision-making in a representative sample of cancer patients.Material and Methods: We conducted a multicenter, epidemiological cross-sectional study with a stratified random sample based on the incidence of cancer diagnoses in Germany. Data were collected between January 2008 and December 2010. Analyses were undertaken between 2017 and 2019. We included 5889 adult cancer patients across all cancer entities and disease stages from 30 acute care hospitals, outpatient facilities, and cancer rehabilitation clinics in five regions in Germany. We used the Control Preferences Scale to assess the preferred level of involvement and the nine-item Shared Decision-Making Questionnaire to assess the perceived level of involvement.Results: About 4020 patients (mean age of 58 years, 51% female) completed the survey. Response rate was 68.3%. About a third each preferred patient-led, shared, or physician-led decision-making. About 50.7% perceived high levels, about a quarter each reported moderate (26.0%) or low (24.3%) levels of shared decision-making. Sex, age, relationship status, education, health care setting, and tumor entity were linked to preferred and/or perceived decision-making. Of those patients who preferred active involvement, about 50% perceived high levels of shared decision-making.Conclusion: The majority of patients with cancer wanted to be involved in medical decisions. Many patients perceived a high level of shared decision-making. However, many patients' level of involvement did not fit their preference. This study provides a solid basis for efforts to improve shared decision-making in German cancer care.

Development of a PDEδ-Targeting PROTACs that Impair Lipid Metabolism.

The prenyl-protein chaperone PDEδ modulates the localization of lipidated proteins in the cell, but current knowledge about its biological function is limited. Small-molecule inhibitors that target the PDEδ prenyl-binding site have proven invaluable in the analysis of biological processes mediated by PDEδ, like KRas cellular trafficking. However, allosteric inhibitor release from PDEδ by the Arl2/3 GTPases limits their application. We describe the development of new proteolysis-targeting chimeras (PROTACs) that efficiently and selectively reduce PDEδ levels in cells through induced proteasomal degradation. Application of the PDEδ PROTACs increased sterol regulatory element binding protein (SREBP)-mediated gene expression of enzymes involved in lipid metabolism, which was accompanied by elevated levels of cholesterol precursors. This finding for the first time demonstrates that PDEδ function plays a role in the regulation of enzymes of the mevalonate pathway.

Posttraumatic stress disorder among cancer patients-Findings from a large and representative interview-based study in Germany.

OBJECTIVE: In order to optimize psycho-oncologic care for patients with severe stressor-related symptomatology, we aimed to provide (a) valid and generalizable prevalence rates of posttraumatic stress disorder (PTSD) in oncological patients and (b) the percentage of PTSD cases elicited by cancer-related events. METHODS: This multi-center study was based on a representative sample of patients across cancer types. A diagnostic interview (CIDI-O) was used to assess PTSD according to DSM-IV. We first describe type and frequency of potentially traumatic events (A1-events) and the degree to which they meet the trauma criteria (A2-events). Subsequently, we present adjusted prevalence rates of PTSD and explore the proportion of patients with cancer-related PTSD. RESULTS: Four thousand twenty patients participated (response rate: 68 %), and 2141 completed the diagnostic interview; 1641 patients reported at least one A1-event, of whom 16% (n = 257) reported cancer-related events. Ninety-one percent (n = 232) of theses cancer-related events qualified as A2-events. Across cancer types, the adjusted 4-week prevalence of PTSD was 2.0% (95% CI, 1.5-2.7); 9% (n = 5) of the 4-week PTSD cases were cancer-related. CONCLUSIONS: Across cancer types and treatment settings, few cancer patients fulfilled diagnostic criteria for PTSD. Of those, a mere fraction was attributable to cancer-related events. These robust findings should be taken into account in both research and practice to develop and provide adequate care for cancer patients with severe stressor-related symptomatology.

Prevalence of mental disorders and psychosocial distress in German adolescent and young adult cancer patients (AYA).

OBJECTIVE: This study provides prevalence data of mental disorders (4-week, 1-year, lifetime) and psychological distress in Adolescent and Young Adult (AYAs) with cancer. METHODS: We included an AYA subsample (15 to 39 year olds; diagnosed within the last 5 years) extracted from a larger sample (4.020 cancer patients) who had been recruited for an epidemiological study across all major tumor entities. Participants were assessed with a depression screener (PHQ-9). Following that, 50% of the participants who scored below the cutoff of 9 and all patients who scored above were assessed using the Composite International Diagnostic Interview for Oncology (CIDI-O). Patients also completed an anxiety screener (GAD-7). RESULTS: A total of 302 AYA (167 completed CIDI-O) were identified. With regard to psychological distress, 29.5% of the AYA had increased depression symptoms (PHQ-9), and 20.8% had increased anxiety symptoms (GAD-7). Gender and age were associated with psychological distress, with women and older AYA being found to have higher distress. The 4-week prevalence of mental disorders of any kind was 46.7% (95%-CI:39%-55%). Anxiety (24.4%; 95%-CI:20%-36%) and adjustment disorders (14.1%; 95%-CI:9%-19%) had the highest prevalence rates. The lowest prevalence rates were reported for alcohol dependence (0.8%; 95%-CI:0%-2%) and somatoform disorders (3.7%; 95%-CI:1%-7%). The 1-year-prevalence was 55.4% (CI:47.36-62.64), and the lifetime-prevalence was 69.5% (CI: 62.29-77.06). CONCLUSION: Our findings may sensitize clinicians to the possible presence of mental disorders in AYA. The results indicate that there is a strong need for psycho-oncological interventions designed to improve mental health in AYAs with cancer at all stages of medical care.

The Generalized Anxiety Disorder Screener (GAD-7) and the anxiety module of the Hospital and Depression Scale (HADS-A) as screening tools for generalized anxiety disorder among cancer patients.

OBJECTIVE: Anxiety in cancer patients may represent a normal psychological reaction. To detect patients with pathological levels, appropriate screeners with established cut-offs are needed. Given that previous research is sparse, we investigated the diagnostic accuracy of 2 frequently used screening tools in detecting generalized anxiety disorder (GAD). METHODS: We used data of a multicenter study including 2141 cancer patients. Diagnostic accuracy was investigated for the Generalized Anxiety Disorder Screener (GAD-7) and the anxiety module of the Hospital Anxiety and Depression Scale (HADS-A). GAD, assessed with the Composite International Diagnostic Interview for Oncology, served as a reference standard. Overall accuracy was measured with the area under the receiver operating characteristics curve (AUC). The AUC of the 2 screeners were statistically compared. We also calculated accuracy measures for selected cut-offs. RESULTS: Diagnostic accuracy could be interpreted as adequate for both screeners, with an identical AUC of .81 (95% CI: .79-.82). Consequently, the 2 screeners did not differ in their performance (P = .86). The best balance between sensitivity and specificity was found for cut-offs ≥7 (GAD-7) and ≥8 (HADS-A). The officially recommended thresholds for the GAD-7 (≥ 10) and the HADS-A (≥11) showed low sensitivities of 55% and 48%, respectively. CONCLUSIONS: The GAD-7 and HADS-A showed AUC of adequate diagnostic accuracy and hence are applicable for GAD screening in cancer patients. Nevertheless, the choice of optimal cut-offs should be carefully evaluated.

Luciferase Advisor: High-Accuracy Model To Flag False Positive Hits in Luciferase HTS Assays.

Firefly luciferase is an enzyme that has found ubiquitous use in biological assays in high-throughput screening (HTS) campaigns. The inhibition of luciferase in such assays could lead to a false positive result. This issue has been known for a long time, and there have been significant efforts to identify luciferase inhibitors in order to enhance recognition of false positives in screening assays. However, although a large amount of publicly accessible luciferase counterscreen data is available, to date little effort has been devoted to building a chemoinformatic model that can identify such molecules in a given data set. In this study we developed models to identify these molecules using various methods, such as molecular docking, SMARTS screening, pharmacophores, and machine learning methods. Among the structure-based methods, the pharmacophore-based method showed promising results, with a balanced accuracy of 74.2%. However, machine-learning approaches using associative neural networks outperformed all of the other methods explored, producing a final model with a balanced accuracy of 89.7%. The high predictive accuracy of this model is expected to be useful for advising which compounds are potential luciferase inhibitors present in luciferase HTS assays. The models developed in this work are freely available at the OCHEM platform at http://ochem.eu .

Quality of life in cancer patients-a comparison of inpatient, outpatient, and rehabilitation settings.

PURPOSE: The aim of this study was to compare quality of life (QoL) data from cancer patients in different clinical settings with data from the general population. METHODS: A sample of 4020 German cancer patients (1735 inpatients, 1324 outpatients, 961 participants in rehabilitation treatment) was tested with the EORTC QLQ-C30. RESULTS: Compared with the general population, cancer patients reported markedly worse QoL. There were clinically significant differences on all 15 scales of the EORTC QLQ-C30 (except one). For the sum score, averaging across 13 scales, the effect size of the difference between cancer patients and the general population was d = 1.16. Inpatients reported the greatest detriments to QoL, followed by the rehabilitation patients and the outpatients (mean sum scores 68.6, 71.0, and 72.3, respectively, compared with 89.2 in the general population). Mean scores for different groups of cancer sites are given separately for the three settings. CONCLUSION: The detriments to QoL were stronger than in comparable studies conducted on data from clinical trials. Since these detriments were found in all three settings to a similar degree, health care providers should offer their services not only to inpatients but to outpatients and patients treated in rehabilitation clinics as well. The data can be used for QoL comparisons of assessments from different settings.

Identification of Two Secondary Ligand Binding Sites in 14-3-3 Proteins Using Fragment Screening.

Proteins typically interact with multiple binding partners, and often different parts of their surfaces are employed to establish these protein-protein interactions (PPIs). Members of the class of 14-3-3 adapter proteins bind to several hundred other proteins in the cell. Multiple small molecules for the modulation of 14-3-3 PPIs have been disclosed; however, they all target the conserved phosphopeptide binding channel, so that selectivity is difficult to achieve. Here we report on the discovery of two individual secondary binding sites that have been identified by combining nuclear magnetic resonance-based fragment screening and X-ray crystallography. The two pockets that these fragments occupy are part of at least three physiologically relevant and structurally characterized 14-3-3 PPI interfaces, including those with serotonin N-acetyltransferase and plant transcription factor FT. In addition, the high degree of conservation of the two sites implies their relevance for 14-3-3 PPIs. This first identification of secondary sites on 14-3-3 proteins bound by small molecule ligands might facilitate the development of new chemical tool compounds for more selective PPI modulation.

The Hospital Anxiety and Depression Scale (HADS) and the 9-item Patient Health Questionnaire (PHQ-9) as screening instruments for depression in patients with cancer.

BACKGROUND: Depression screening in patients with cancer is recommended by major clinical guidelines, although the evidence on individual screening tools is limited for this population. Here, the authors assess and compare the diagnostic accuracy of 2 established screening instruments: the depression modules of the 9-item Patient Health Questionnaire (PHQ-9) and the Hospital Anxiety and Depression Scale (HADS-D), in a representative sample of patients with cancer. METHODS: This multicenter study was conducted with a proportional, stratified, random sample of 2141 patients with cancer across all major tumor sites and treatment settings. The PHQ-9 and HADS-D were assessed and compared in terms of diagnostic accuracy and receiver operating characteristic (ROC) curves for Diagnostic and Statistical Manual of Mental Disorders, 4th edition diagnosis of major depressive disorder using the Composite International Diagnostic Interview for Oncology as the criterion standard. RESULTS: The diagnostic accuracy of the PHQ-9 and HADS-D was fair for diagnosing major depressive disorder, with areas under the ROC curves of 0.78 (95% confidence interval, 0.76-0.79) and 0.75 (95% confidence interval, 0.74-0.77), respectively. The 2 questionnaires did not differ significantly in their areas under the ROC curves (P = .15). The PHQ-9 with a cutoff score ≥7 had the best screening performance, with a sensitivity of 83% (95% confidence interval, 78%-89%) and a specificity of 61% (95% confidence interval, 59%-63%). The American Society of Clinical Oncology guideline screening algorithm had a sensitivity of 44% (95% confidence interval, 36%-51%) and a specificity of 84% (95% confidence interval, 83%-85%). CONCLUSIONS: In patients with cancer, the screening performance of both the PHQ-9 and the HADS-D was limited compared with a standardized diagnostic interview. Costs and benefits of routinely screening all patients with cancer should be weighed carefully. Cancer 2017;123:4236-4243. © 2017 American Cancer Society.

Anxiety and depression in working-age cancer survivors: a register-based study.

BACKGROUND: Anxiety and depression can be a long-term strain in cancer survivors. Little is known about the emotional situation of cancer survivors who have to deal with work- and family-related issues. The purpose of this study was to investigate anxiety and depression in working-age cancer survivors and associated factors. METHODS: A register-based sample of 3370 cancer survivors (25 to 55 years at time of diagnosis) diagnosed up to six years prior to the survey was recruited from two German cancer registries. Demographic and medical characteristics as well as self-reported measures were used. RESULTS: Overall, approximately 40% of the survivors reported moderate to high anxiety scores and approximately 20% reported moderate to high depression scores. Compared to the general population, working-age cancer survivors were more anxious but less depressed (p < .001). Subgroups with regard to time since diagnosis did not differ in anxiety or depression. Anxiety and depression in cancer survivors were associated with various variables. Better social support, family functioning and physical health were associated with lower anxiety and depression. CONCLUSIONS: Overall, we found higher anxiety levels in cancer survivors of working-age than in the general population. A considerable portion of cancer survivors reported moderate to high levels of anxiety and depression. The results indicate the need for psychosocial screening and psycho-oncological support e.g. in survivorship programs for working-age cancer survivors. Assessing the physical health, social support and family background might help to identify survivors at risk for higher emotional distress.

Effectiveness of case management as a cross-sectoral healthcare provision for women with breast cancer.

OBJECTIVE: Case management (CM) programs are intended to improve care coordination for cancer patients. This quasi-experimental, controlled study evaluated whether such a program was effective in improving health-related quality of life and reducing the psychological distress of breast cancer patients. METHODS: For the study, 126 patients with CM and 118 patients with treatment as usual (TAU) were surveyed at baseline, a 6-month follow-up and a 12-month follow-up. Comparisons of the two groups with regard to quality of life (Short Form-8, European Organization for Research and Treatment of Cancer-11; primary outcome) and psychological distress (Hospital Anxiety and Depression Scale, distress thermometer; secondary outcome) were conducted. RESULTS: Univariate t-tests regarding the primary and secondary outcomes demonstrated improvements in the relevant outcomes at the 6-month and 12-month follow-ups for the intervention group as well as for the control group. An analysis of covariance revealed that the controls showed a higher level of physical quality of life at the 12-month follow-up than the other time points and no differences at 6 months after the baseline. CONCLUSIONS: The tested CM model did not improve the quality of life or psychological well-being of the patients beyond treatment as usual. Possible reasons include that the treatment was already of high standards in the control group or that there are possibly different impacts than found in the literature regarding different forms of organization in CM. The need for and the tailoring of this CM model as well as the transfer of CM to other oncological indications remain to be clarified. Copyright © 2016 John Wiley & Sons, Ltd.

Cancer-and-treatment-specific distress and its impact on posttraumatic stress in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT).

BACKGROUND: In this prospective multicenter study, we investigated cancer-and-treatment-specific distress (CTXD) and its impact on symptoms of posttraumatic stress disorder (PTSD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: Patients were consulted before (T0, N = 239), 3 (T1, N = 150), and 12 months (T2, N = 102) after HSCT. Medical (eg, diagnosis and pretreatment) and demographic information, CTXD and PTSD (PCL-C) were assessed. RESULTS: Random intercept models revealed that the sum score of CTXD was highest pre-HSCT (T0), decreased by T1 (γ = -.18, 95% CI [-.26/-.09]), and by T2 (γ = -.10, 95% CI [-.20/-.00]). Uncertainty, family strain, and health burden were rated most distressing during HSCT. Uncertainty and family strain decreased from T0 to T1 (γ = -.30, 95% CI [-.42/-.17]; γ = -.10, 95% CI [-.20/-.00]) and health burden from T1 to T2 (γ = -.21, 95% CI [-.36/.05]). Women were more likely to report uncertainty (γ = .38, 95% CI [.19/.58]), family strain (γ = .38, 95% CI [.19/.58]), and concerns regarding appearance and sexuality (γ = .31, 95% CI [.14/.47]) than men. Uncertainty (γ = .18, 95% CI [.12/.24]), appearance and sexuality (γ = .09, 95% CI [.01/.16]), and health burden (γ = .21, 95% CI [.14/.27]) emerged as predictors of PTSD symptomatology across the 3 assessment points. CONCLUSIONS: Our data provide first evidence regarding the course of 6 dimensions of CTXD during HSCT and their impact on PTSD symptomatology. Specifically, results emphasize the major burden of uncertainty pre-HSCT and the impact of uncertainty and concerns regarding appearance and sexuality on PTSD symptomatology.

Utilization of professional psychological care in a large German sample of cancer patients.

OBJECTIVE: Although one-third of cancer patients are perceived to have a need for psychological support based on the percentage of mental disorders, little is known about the actual utilization of psychological care in cancer. We aimed to assess cancer patients' reported use of psychological care and its correlates in a large, representative sample. METHODS: In a multicenter, cross-sectional study in Germany, 4020 cancer patients (mean age 58 years, 51% women) were evaluated. We obtained self-reports of use of psychotherapy and psychological counseling. We measured distress with the Distress Thermometer, symptoms of depression with the Patient Health Questionnaire, anxiety with the Generalized Anxiety Disorder Scale, and social support with the Illness-specific Social Support Scale. In a subsample of 2141, we evaluated the presence of a mental disorder using the Composite International Diagnostic Interview. RESULTS: In total, 28.9% (95% confidence interval 27.4%-30.4%) reported having used psychotherapy or psychological counseling or both because of distress due to cancer. Independent correlates of utilization included age (odds ratio [OR] = 0.97 per year], sex (male, OR = 0.55), social support (OR = 0.96), symptoms of depression (OR = 1.04) and anxiety (OR = 1.08), the diagnosis of a mental disorder (OR = 1.68), and a positive attitude toward psychosocial support (OR = 1.27). Less than half of those currently diagnosed with a mental disorder reported having taken up psychological support offers. CONCLUSION: Special efforts should be made to reach populations that report low utilization of psychological care in spite of having a need for support.

Lifetime prevalence of mental disorders among first and second generation individuals with Turkish migration backgrounds in Germany.

BACKGROUND: This paper focuses on the lifetime prevalence of mental disorders in individuals with Turkish migration backgrounds in Germany, as there is a lack of reliable epidemiological data on this subject. METHODS: In total, 662 adults with Turkish migration backgrounds were interviewed in Hamburg and Berlin by trained, bilingual interviewers using the computerized Composite International Diagnostic Interview (CIDI DIA-X Version 2.8) to assess diagnoses according to the DSM-IVTR. RESULTS: The analyses showed a weighted lifetime prevalence of 78.8% for any mental disorder, 21.6% for more than one and 7.3% for five or more disorders. Any mood disorder (41.9%), any anxiety disorder (35.7%) and any somatoform disorder/syndrome (33.7%) had the highest prevalences. Despite the sociodemographic differences between the first and second generations, there were no significant differences in the lifetime prevalence between generations, with the exception of any bipolar disorder. Female gender, older age and no current partnership were significantly associated with the occurrence of any mood disorder. CONCLUSIONS: Overall, the results indicate a high lifetime prevalence in individuals with Turkish migration backgrounds in Germany. These initial data are highly relevant to the German clinical and psychosocial healthcare system; however, the methodological limitations and potential biases should be considered when interpreting the results.

[Breaking Bad News to Cancer Patients: Content, Communication Preferences and Psychological Distress]. / Die Kommunikation schlechter Nachrichten bei Krebspatienten: Inhalte, Kommunikationspräferenzen und psychische Belastungen.

Objectives Breaking bad news can be a very distressing situation for both patients and physicians. Physician communication behavior should therefore match patients' communication preferences. The aim of this study was to characterize the content of bad news from the patients' perspective. Patients' preferences for communication of bad news as well as the fit to communication behavior displayed by physicians were also investigated. Finally, consequences of a mismatch between patients' preferences and physician communication were investigated in relation to psychological distress in patients. Methods The sample consisted of N=270 cancer patients (mean age=56.8 years, 48% female) with various cancer entities and different stages of disease (n=115 patients with early stage of cancer, n=155 patients with advanced cancer). The content of bad news was assessed with a specifically developed list of questions. The Measure of Patients' Preferences Scale (MPP) was used to assess patients' preferences for communication of bad news. Patients further completed the NCCN Distress Thermometer (cancer specific distress), the Hospital Anxiety and Depression Scale (HADS- anxiety and depression) and the Demoralization Scale (DS-Scale) to gain information about psychological distress. Results Patients with early stage breast cancer received bad news M=1.6 times (SD=1.1, range: 1-5), patients with advanced cancers M=2.1 times (SD=1.6, range: 1-12). For 77% of early stage cancer patients and 70% of advanced cancer patients, the subjectively worst consultation was receiving the diagnosis and discussing treatment options. Patients' most important communication preferences were physicians' clinical competence and patient-centered communication, clear and direct communication and asking about patients information preferences. Patients in advanced stages report significantly more (29%) unmet communication needs than patients' in early stages (20%; p<0.01). Breaking bad news without considering patients' preferences was associated with higher psychological distress in patients. Conclusion Physicians should communicate in a patient-centered way to reduce mismatch with patients' preferences and thereby potentially reduce patients' psychological distress.