Objectives This study aimed to (i) investigate cancer survivor's employment status one year after the completion of a medical rehabilitation program and (ii) identify demographic, cancer, and ...psychosocial, treatment-, and work-related predictors of return to work (RTW) and time until RTW. Methods A total of 1520 eligible patients were consecutively recruited on average 11 months post diagnosis and assessed at the beginning (t 0 ) (N=1148) and end of rehabilitation (t 1 ) (N=1060) and 12 months after rehabilitation (t 2 ) (N=750). Participants completed validated measures assessing functional impairments, pain, anxiety, depression, quality of life, social support, and work-related characteristics including work ability, sick leave absence, job requirements, work satisfaction, self-perceived employer accommodation, and perceived job loss. Physicians estimated the degree of cancer-entity-specific functional impairment. Results In a mean time of six weeks after rehabilitation, 568 patients (76%) had returned to work. The multivariate hierarchical logistic regression analysis indicated that baseline RTW intention odds ratio (OR) 6.22,95% confidence interval (95% CI) 1.98-19.51, perceived employer accommodation (OR 1.93, 95% CI 0.33-0.99), high job requirements (OR=1.84, 95% CI 1.02-3.30), cancer recurrence or progression (OR=0.27,95% CI 0.12 — 0.63), baseline sick leave absence (OR=0.26, 95% CI 0.09-0.77), and problematic social interactions (OR=0.58, 95% CI 0.33-0.99) emerged as significant predictors for RTW. The explained variance of the total model was Nagelkerke's R 2 =0.59 (P<0.001). Conclusion Our findings emphasize the high relevance of motivational factors. Occupational motivation and skepticism towards returning to work should be carefully assessed at the planning of the rehabilitation program.
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) system
. 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 OXPHOS
, 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.
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 global prevalence of hepatitis C virus (HCV) infection and the serious consequences associated with the chronic state of the disease have become a worldwide health problem. A combination therapy ...comprising Interferon-alpha and Ribavirin represents the current standard treatment for chronic HCV infection, although it has demonstrated limited success and causes serious side effects. Promising alternative approaches toward the control of HCV infection include the development of small molecule inhibitors of viral enzymes interfering with the essential steps in the life cycle of the virus. In this review we will focus on inhibitors of the HCV-encoded NS5B RNA-dependent RNA polymerase (NS5B RdRp) which is essential for viral replication and has been recognized as a prime target for therapeutic intervention.
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.
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.
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.
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.
Neurons of the respiratory network in the lower brainstem express a variety of serotonin receptors (5-HTRs) that act primarily through adenylyl cyclase. However, there is one receptor family ...including 5-HT(2A), 5-HT(2B), and 5-HT(2C) receptors that are directed towards protein kinase C (PKC). In contrast to 5-HT(2A)Rs, expression and function of 5-HT(2B)Rs within the respiratory network are still unclear. 5-HT(2B)R utilizes a Gq-mediated signaling cascade involving calcium and leading to activation of phospholipase C and IP3/DAG pathways. Based on previous studies, this signal pathway appears to mediate excitatory actions on respiration. In the present study, we analyzed receptor expression in pontine and medullary regions of the respiratory network both at the transcriptional and translational level using quantitative RT-PCR and self-made as well as commercially available antibodies, respectively. In addition we measured effects of selective agonists and antagonists for 5-HT(2A)Rs and 5-HT(2B)Rs given intra-arterially on phrenic nerve discharges in juvenile rats using the perfused brainstem preparation. The drugs caused significant changes in discharge activity. Co-administration of both agonists revealed a dominance of the 5-HT(2B)R. Given the nature of the signaling pathways, we investigated whether intracellular calcium may explain effects observed in the respiratory network. Taken together, the results of this study suggest a significant role of both receptors in respiratory network modulation.
Existential distress is an important factor affecting psychological well-being in cancer patients. We studied occurrence and predictors of demoralization, a syndrome of existential distress, in ...particular the interaction of age, gender, and curative vs. palliative treatment phase.
A cross-sectional sample of N = 750 patients with different tumor sites was recruited from in- and outpatient treatment facilities. Patients completed the following self-report questionnaires: Demoralization Scale, Patient Health Questionnaire-9, Illness-Specific Social Support Scale Short Version-8, and physical problems list of the NCCN Distress Thermometer. Moderated multiple regression analyses were conducted.
We found high demoralization in 15% and moderate demoralization in 8% of the sample. Curative vs. palliative treatment phase moderated the impact of age and gender on demoralization (three-way interaction: b = 1.30, P = .02): the effect of age on demoralization was negative for women receiving palliative treatment (b = -.26, P = .02) and positive for men receiving palliative treatment (b = .25, P = .03). Effects of age and gender were not significant among patients receiving curative treatment. Female gender was associated with higher demoralization among younger patients receiving palliative treatment only. Analyses were controlled for significant effects of the number of physical problems (b = 6.10, P<.001) and social support (b = -3.17, P<.001).
Existential distress in terms of demoralization is a relevant problem within the spectrum of cancer-related distress. It is associated with a complex interaction of demographic and medical patient characteristics; existential challenges related to palliative treatment may exacerbate the impact of age- and gender-related vulnerability factors on demoralization. Psychosocial interventions should acknowledge this interaction in order to address the individual nature of existential distress in subgroups 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.
Abstract Context The concept of demoralization has been widely used to describe states of existential distress and a self-perceived incapacity to deal effectively with a specific stressful situation. ...Objectives To evaluate the psychometric properties of the German adaptation of the Demoralization Scale (DS) in patients with advanced cancer. Methods Participants with heterogeneous tumor sites were recruited in several treatment and rehabilitation facilities. Concurrent and divergent validity of the DS was analyzed through associations with and group differences between measures of distress, depression, anxiety, and meaning-related life attitudes. Results From a total sample of 1102 patients, 516 individuals (45%) with advanced cancer were enrolled (male 53%, median age 58 years range 18–88, breast cancer 21%, prostate cancer 17%). The total mean score of the DS was 29.8 (SD = 10.41). Four factors were extracted by exploratory factor analysis, which accounted for 59% of the variation (Cronbach α = 0.84): loss of meaning and purpose (α = 0.88), disheartenment (α = 0.88), dysphoria (α = 0.80), and sense of failure (α = 0.76). DS dimensions shared between 12% and 62% of the variance. Demoralization was significantly associated with anxiety ( r = 0.71), depression ( r = 0.61), and distress ( r = 0.42). Fifty-seven percent of patients had high distress, 24% depression, and 11% high anxiety. According to different cutoff values, between 16% and 39% were seriously demoralized and 73% had moderate levels of demoralization. Between 5% and 20% of patients were seriously demoralized but not clinically depressed; 60% of patients with moderate levels of demoralization had no depression. Conclusion Results provide further evidence that the DS is a valid and reliable instrument of high clinical relevance in patients with advanced cancer.
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