Altered brain perfusion and oxygen levels relate to sleepiness and attention in post-COVID syndrome.

OBJECTIVE: Persisting neurological symptoms after COVID-19 affect up to 10% of patients and can manifest in fatigue and cognitive complaints. Based on recent evidence, we evaluated whether cerebral hemodynamic changes contribute to post-COVID syndrome (PCS). METHODS: Using resting-state functional magnetic resonance imaging, we investigated brain perfusion and oxygen level estimates in 47 patients (44.4 ± 11.6 years; F:M = 38:9) and 47 individually matched healthy control participants. Group differences were calculated using two-sample t-tests. Multivariable linear regression was used for associations of each regional perfusion and oxygen level measure with cognition and sleepiness measures. Exploratory hazard ratios were calculated for each brain metric with clinical measures. RESULTS: Patients presented with high levels of fatigue (79%) and daytime sleepiness (45%). We found widespread decreased brain oxygen levels, most evident in the white matter (false discovery rate adjusted-p-value (p-FDR) = 0.038) and cortical grey matter (p-FDR = 0.015). Brain perfusion did not differ between patients and healthy participants. However, delayed patient caudate nucleus perfusion was associated with better executive function (p-FDR = 0.008). Delayed perfusion in the cortical grey matter and hippocampus were associated with a reduced risk of daytime sleepiness (hazard ratio (HR) = 0.07, p = 0.037 and HR = 0.06, p = 0.034). Decreased putamen oxygen levels were associated with a reduced risk of poor cognitive outcome (HR = 0.22, p = 0.019). Meanwhile, lower thalamic oxygen levels were associated with a higher risk of cognitive fatigue (HR = 6.29, p = 0.017). INTERPRETATION: Our findings of lower regional brain blood oxygen levels suggest increased cerebral metabolism in PCS, which potentially holds a compensatory function. These hemodynamic changes were related to symptom severity, possibly representing metabolic adaptations.

Characteristic functional connectome related to Post-COVID-19 syndrome.

Post-COVID-19 syndrome is a serious complication following SARS-CoV-2 infection, characterized primarily by fatigue and cognitive complaints. Although first metabolic and structural imaging alterations in Post-COVID-19 syndrome have been identified, their functional consequences remain unknown. Thus, we explored the impact of Post-COVID-19 syndrome on the functional connectome of the brain providing a deeper understanding of pathophysiological mechanisms. In a cross-sectional observational study, resting-state functional magnetic resonance imaging data of 66 patients with Post-COVID-19 syndrome after mild infection (mean age 42.3 years, 57 female) and 57 healthy controls (mean age 42.1 years, 38 female) with a mean time of seven months after acute COVID-19 were analysed using a graph theoretical approach. Network features were quantified using measures including mean distance, nodal degree, betweenness and Katz centrality, and compared between both groups. Graph measures were correlated with clinical measures quantifying fatigue, cognitive function, affective symptoms and sleep disturbances. Alterations were mainly found in the brainstem, olfactory cortex, cingulate cortex, thalamus and cerebellum on average seven months after SARS-CoV-2 infection. Additionally, strong correlations between fatigue severity, cognitive functioning and daytime sleepiness from clinical scales and graph measures were observed. Our study confirms functional relevance of brain imaging changes in Post-COVID-19 syndrome as mediating factors for persistent symptoms and improves our pathophysiological understanding.

Predictors of non-recovery from fatigue and cognitive deficits after COVID-19: a prospective, longitudinal, population-based study.

Background: Despite the high prevalence and major disability associated with fatigue and cognitive deficits after SARS-CoV-2 infection, little is known about long-term trajectories of these sequelae. We aimed to assess long-term trajectories of these conditions and to identify risk factors for non-recovery. Methods: We analyzed longitudinal data from the population-based COVIDOM/NAPKON-POP cohort in Germany. Participants with confirmed SARS-CoV-2 infection were assessed at least 6 months (baseline) and again at least 18 months (follow-up) after infection using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale (cutoff ≤ 30) and the Montreal Cognitive Assessment (MoCA, cutoff ≤ 25). Predictors of recovery from fatigue or cognitive deficits between assessments were identified through univariate and multivariable logistic regression models. The COVIDOM study is registered at the German registry for clinical studies (DRKS00023742) and at ClinicalTrials.gov (NCT04679584). Findings: Between 15 November 2020 and 9 May 2023, a total of 3038 participants were assessed at baseline (median 9 months after infection) and 83% responded to invitations for follow-up (median 26 months after infection). At baseline, 21% (95% confidence interval (CI) [20%, 23%]) had fatigue and 23% (95% CI [22%, 25%]) had cognitive deficits according to cutoff scores on the FACIT-Fatigue or MoCA. Participants with clinically relevant fatigue (at baseline) showed significant improvement in fatigue scores at follow-up (Hedges' g [95% CI] = 0.73 [0.60, 0.87]) and 46% (95% CI [41%, 50%]) had recovered from fatigue. Participants with cognitive deficits showed a significant improvement in cognitive scores (g [95% CI] = 1.12 [0.90, 1.33]) and 57% (95% CI [50%, 64%]) had recovered from cognitive deficits. Patients with fatigue exhibiting a higher depressive symptom burden and/or headache at baseline were significantly less likely to recover. Significant risk factors for cognitive non-recovery were male sex, older age and <12 years of school education. Importantly, SARS-CoV-2 reinfection had no significant impact on recovery from fatigue or cognitive deficits. Interpretation: Fatigue and cognitive deficits are common sequelae after SARS-CoV-2 infection. These syndromes improved over time and about half of the patients recovered within two years. The identified risk factors for non-recovery from fatigue and cognitive deficits could play an important role in shaping targeted strategies for treatment and prevention. Funding: Funded by the German Federal Ministry of Education and Research (BMBF; grant number 01KX2121) and German Research Foundation (DFG) Excellence Cluster "Position Medicine in Information".

Analysis of acute COVID-19 including chronic morbidity: protocol for the deep phenotyping National Pandemic Cohort Network in Germany (NAPKON-HAP).

BACKGROUND: The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic causes a high burden of acute and long-term morbidity and mortality worldwide despite global efforts in containment, prophylaxis, and therapy. With unprecedented speed, the global scientific community has generated pivotal insights into the pathogen and the host response evoked by the infection. However, deeper characterization of the pathophysiology and pathology remains a high priority to reduce morbidity and mortality of coronavirus disease 2019 (COVID-19). METHODS: NAPKON-HAP is a multi-centered prospective observational study with a long-term follow-up phase of up to 36 months post-SARS-CoV-2 infection. It constitutes a central platform for harmonized data and biospecimen for interdisciplinary characterization of acute SARS-CoV-2 infection and long-term outcomes of diverging disease severities of hospitalized patients. RESULTS: Primary outcome measures include clinical scores and quality of life assessment captured during hospitalization and at outpatient follow-up visits to assess acute and chronic morbidity. Secondary measures include results of biomolecular and immunological investigations and assessment of organ-specific involvement during and post-COVID-19 infection. NAPKON-HAP constitutes a national platform to provide accessibility and usability of the comprehensive data and biospecimen collection to global research. CONCLUSION: NAPKON-HAP establishes a platform with standardized high-resolution data and biospecimen collection of hospitalized COVID-19 patients of different disease severities in Germany. With this study, we will add significant scientific insights and provide high-quality data to aid researchers to investigate COVID-19 pathophysiology, pathology, and chronic morbidity.

The T1-weighted/T2-weighted ratio as a biomarker of anti-NMDA receptor encephalitis.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis rarely causes visible lesions in conventional MRI, yet advanced imaging detects extensive white matter damage. To improve prognostic capabilities, we evaluate the T1-weighted/T2-weighted (T1w/T2w) ratio, a measure of white matter integrity computable from clinical MRI sequences, in NMDAR encephalitis and examine its associations with cognitive impairment. METHODS: T1-weighted and T2-weighted MRI were acquired cross-sectionally at 3 Tesla in 53 patients with NMDAR encephalitis (81% women, mean age 29 years) and 53 matched healthy controls. Quantitative and voxel-wise group differences in T1w/T2w ratios and associations with clinical and neuropsychological outcomes were assessed. P-values were false discovery rate (FDR) adjusted where multiple tests were conducted. RESULTS: Patients with NMDAR encephalitis had significantly lower T1w/T2w ratios across normal appearing white matter (p=0.009, Hedges' g=-0.51), which was associated with worse verbal episodic memory performance (r=0.39, p=0.005, p(FDR)=0.026). White matter integrity loss was observed in the corticospinal tract, superior longitudinal fascicle, optic radiation and callosal body with medium to large effects (Cohen's d=[0.42-1.17]). In addition, patients showed decreased T1w/T2w ratios in the hippocampus (p=0.002, p(FDR)=0.005, Hedges' g=-0.62), amygdala (p=0.002, p(FDR)=0.005, Hedges' g=-0.63) and thalamus (p=0.010, p(FDR)=0.019, Hedges' g=-0.51). CONCLUSIONS: The T1w/T2w ratio detects microstructural changes in grey and white matter of patients with NMDAR encephalitis that correlate with cognitive performance. Computable from conventional clinical MRI sequences, this measure shows promise in bridging the clinico-radiological dissociation in NMDAR encephalitis and could serve as an imaging outcome measure in clinical trials.

Structural brain changes in patients with post-COVID fatigue: a prospective observational study.

Background: Post-COVID syndrome is a severe long-term complication of COVID-19. Although fatigue and cognitive complaints are the most prominent symptoms, it is unclear whether they have structural correlates in the brain. We therefore explored the clinical characteristics of post-COVID fatigue, describe associated structural imaging changes, and determine what influences fatigue severity. Methods: We prospectively recruited 50 patients from neurological post-COVID outpatient clinics (age 18-69 years, 39f/8m) and matched non-COVID healthy controls between April 15 and December 31, 2021. Assessments included diffusion and volumetric MR imaging, neuropsychiatric, and cognitive testing. At 7.5 months (median, IQR 6.5-9.2) after the acute SARS-CoV-2 infection, moderate or severe fatigue was identified in 47/50 patients with post-COVID syndrome who were included in the analyses. As a clinical control group, we included 47 matched multiple sclerosis patients with fatigue. Findings: Our diffusion imaging analyses revealed aberrant fractional anisotropy of the thalamus. Diffusion markers correlated with fatigue severity, such as physical fatigue, fatigue-related impairment in everyday life (Bell score) and daytime sleepiness. Moreover, we observed shape deformations and decreased volumes of the left thalamus, putamen, and pallidum. These overlapped with the more extensive subcortical changes in MS and were associated with impaired short-term memory. While fatigue severity was not related to COVID-19 disease courses (6/47 hospitalised, 2/47 with ICU treatment), post-acute sleep quality and depressiveness emerged as associated factors and were accompanied by increased levels of anxiety and daytime sleepiness. Interpretation: Characteristic structural imaging changes of the thalamus and basal ganglia underlie the persistent fatigue experienced by patients with post-COVID syndrome. Evidence for pathological changes to these subcortical motor and cognitive hubs provides a key to the understanding of post-COVID fatigue and related neuropsychiatric complications. Funding: Deutsche Forschungsgemeinschaft (DFG) and German Ministry of Education and Research (BMBF).

Interconnectivity of fear of progression and generalized anxiety - Network analysis among a sample of hematological cancer survivors.

PURPOSE: Fear of cancer progression and recurrence (FoP) and generalized anxiety disorder (GAD) are syndromes commonly seen in cancer patients. This study applied network analysis to investigate how symptoms of both concepts are interconnected. METHODS: We used cross-sectional data from hematological cancer survivors. A regularized Gaussian graphical model including symptoms of FoP (FoP-Q) and GAD (GAD-7) was estimated. We investigated (i) the overall network structure and (ii) tested on pre-selected items whether both syndromes could be differentiated based on their worry content (cancer related vs. generalized). For this purpose, we applied a metric named bridge expected influence (BEI). Lower values mean that an item is only weakly connected with the items of the other syndrome, which can be an indication of its distinctive characteristic. RESULTS: Out of 2001 eligible hematological cancer survivors, 922 (46%) participated. The mean age was 64 years and 53% were female. The mean partial correlation within each construct (GAD: r = .13; FoP: r = .07) was greater than between both (r = .01). BEI values among items supposed to discriminate between the constructs (e.g., worry about many things within GAD and fear not to endure treatment within FoP) were among the smallest so our assumptions were confirmed. CONCLUSIONS: Our findings based on the network analysis support the hypothesis that FoP and GAD are different concepts within oncology. Our exploratory data needs to be validated in future longitudinal studies.

The German version of the body image scale: Validation and item response analysis in cancer patients.

OBJECTIVE: To translate the cancer-specific Body Image Scale (BIS) into German and assess its psychometric properties. METHODS: The BIS was translated in accordance with current guidelines. In a prospective, cross-sectional two center study (psychosocial counselling center for cancer patients Leipzig, oncological inpatient ward Berlin), we assessed composite reliability and factor structure using confirmatory factor analysis. Additional item response theory (IRT) modelling was performed. Convergent validity was assessed via correlation with the Body Appreciation Scale (BAS) as well as psychological symptom burden (PHQ-9, GAD-2 and Distress Thermometer). Discriminant validity was assessed via demographic and clinical group comparisons. RESULTS: 677 patients participated (response rate 78%). Composite reliability was 0.95 and the one-factor structure was confirmed (standardized root mean square residual = 0.051, average variance extracted ≥50%, no indications of local dependence). In IRT models, all items had a discriminating power above the established threshold of b = 0.5 and relatively high "difficulty" parameters (b = 0.89-2.06). The BIS was negatively correlated with the BAS (rho = -0.62, p < 0.001) and positively with psychological symptom burden (e.g. PHQ-9: rho = 0.49, p < 0.001). Patients who were younger, female, had undergone chemotherapy, radiotherapy or surgery and those who were distressed by fatigue, their appearance or sexual problems had significantly higher BIS scores. CONCLUSION: The German version of the BIS is a valid tool to assess BID in patients with cancer that is now available for clinical or research contexts.

Fatigue and cognitive impairment after COVID-19: A prospective multicentre study.

Background: Reliable estimates of frequency, severity and associated factors of both fatigue and cognitive impairment after COVID-19 are needed. Also, it is not clear whether the two are distinct sequelae of COVID-19 or part of the same syndrome." Methods: In this prospective multicentre study, frequency of post-COVID fatigue and cognitive impairment were assessed in n = 969 patients (535 [55%] female) ≥6 months after SARS-CoV-2 infection with the FACIT-Fatigue scale (cut-off ≤30) and Montreal Cognitive Assessment (≤25 mild, ≤17 moderate impairment) between November 15, 2020 and September 29, 2021 at University Medical Center Schleswig-Holstein, Campus Kiel and University Hospital Würzburg in Germany. 969 matched non-COVID controls were drawn from a pre-pandemic, randomised, Germany-wide population survey which also included the FACIT-Fatigue scale. Associated sociodemographic, comorbid, clinical, psychosocial factors and laboratory markers were identified with univariate and multivariable linear regression models. Findings: On average 9 months after infection, 19% of patients had clinically relevant fatigue, compared to 8% of matched non-COVID controls (p < 0.001). Factors associated with fatigue were female gender, younger age, history of depression and the number of acute COVID symptoms. Among acute COVID symptoms, altered consciousness, dizziness and myalgia were most strongly associated with long-term fatigue. Moreover, 26% of patients had mild and 1% had moderate cognitive impairment. Factors associated with cognitive impairment were older age, male gender, shorter education and a history of neuropsychiatric disease. There was no significant correlation between fatigue and cognitive impairment and only 5% of patients suffered from both conditions. Interpretation: Fatigue and cognitive impairment are two common, but distinct sequelae of COVID-19 with potentially separate pathophysiological pathways. Funding: German Federal Ministry of Education and Research (BMBF).

Psychometric Evaluation of the German Version of the Demoralization Scale-II and the Association Between Demoralization, Sociodemographic, Disease- and Treatment-Related Factors in Patients With Cancer.

Objective: To test the psychometric properties, internal consistency, dimensional structure, and convergent validity of the German version of the Demoralization Scale-II (DS-II), and to examine the association between demoralization, sociodemographic, disease- and treatment-related variables in patients with cancer. Methods: We recruited adult patients with cancer at a Psychosocial Counseling Center and at oncological wards. Participants completed the 16-item DS-II, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Screener-2 (GAD-2), Distress Thermometer (DT), and Body Image Scale (BIS). We analyzed internal consistency of the DS-II using Cronbach's Alpha (α). We tested the dimensional structure of the DS-II with Confirmatory Factor Analyses (CFA). Convergent validity was expressed through correlation coefficients with established measures of psychological distress. The associations between demoralization, sociodemographic, disease- and treatment-related variables were examined with ANOVAs. Results: Out of 942 eligible patients, 620 participated. The average DS-II total score was M = 5.78, SD = 6.34, the Meaning and Purpose subscale M = 2.20, SD = 3.20, and the Distress and Coping Ability subscale M = 3.58, SD = 3.45. Internal consistency ranged from high to excellent with α = 0.93 for the DS-II total scale, α = 0.90 for the Meaning and Purpose subscale, and α = 0.87 for the Distress and Coping Ability subscale. The one-factor and the two-factor model yielded similar model fits, with CFI and TLI ranging between 0.910 and 0.933, SRMR < 0.05. The DS-II correlated significantly with depression (PHQ-9: r = 0.69), anxiety (GAD-2: r = 0.72), mental distress (DT: r = 0.36), and body image disturbance (BIS: r = 0.58). High levels of demoralization were reported by patients aged between 18 and 49 years (M = 7.77, SD = 6.26), patients who were divorced/separated (M = 7.64, SD = 7.29), lung cancer patients (M = 9.29, SD = 8.20), and those receiving no radiotherapy (M = 7.46, SD = 6.60). Conclusion: The DS-II has very good psychometric properties and can be recommended as a reliable tool for assessing demoralization in patients with cancer. The results support the implementation of a screening for demoralization in specific risk groups due to significantly increased demoralization scores.

Assessment of sleep problems with the Insomnia Severity Index (ISI) and the sleep item of the Patient Health Questionnaire (PHQ-9) in cancer patients.

OBJECTIVE: The objectives of this study were to examine sleep problems in cancer patients, to test the psychometric properties of the Insomnia Sleep Index (ISI) in comparison with the sleep item of the Patient Health Questionnaire-9 (PHQ-9), and to analyze disrupting factors which might cause the sleep problems. METHODS: A sample of 1026 mixed-site cancer patients in treatment at a German oncological rehabilitation clinic was examined. RESULTS: The reliability of the ISI was very good (Cronbach's alpha = 0.92), and the results of the confirmatory factor analysis were acceptable. Females reported worse sleep quality (ISI mean: 13.7 ± 6.6) than males (10.7 ± 6.4). Sleep problems as measured with the PHQ-9 sleep item were markedly higher than those in the general population (effect size d = 1.15). Patients reported that, of the factors that disrupted their sleep, psychological factors (brooding, worries) were more relevant than symptom factors (pain, nocturnal urination, or restless legs). CONCLUSIONS: The ISI is effective in detecting sleep problems in cancer patients. Normative studies with the ISI would be helpful for assessing ISI mean scores. Sex differences should be taken into account when groups of patients are compared. The sleep item of the PHQ-9 can be used in epidemiological studies.

COMSKIL: a communication skills training program for medical students.

Objectives: Training communication skills has come to be recognized as a vital aspect of medical school education. A medical communication course based on the COMSKIL Communication Skills Training (CST) Program was developed, integrated into the core curriculum, and evaluated at the Leipzig University Medical School. Methods: Between October 2016 and July 2017, 312 medical students (mean age 21.80 years; 62% male) participated in the medical communication course. Each course unit was evaluated via questionnaires specifically designed to address the theoretical and practical content of the curriculum. The items correspond to the material covered in each course unit. Students responded using a 5-point-Likert scale (1="not at all helpful", 5="extremely helpful") to rate the degree to which the course helped them learn about the subject matter and train the skills covered in the curriculum. Results: The average score for the first part of the course (theoretical foundations) was M=3.69 (SD=0.35). The second part received a similar rating (M=3.84; SD=0.73). The role play exercises with actor-patients received a score of M=4.27 (SD=0.62). In an overall evaluation at the end of the course, students rated the administration of the course (setting, etc), knowledge gained, and skills trained with a score of M=4.11 (SD=0.66). The role play exercises received an overall score of M=4.36 (SD=0.61). Conclusion: A new curriculum for teaching medical students patient-physician communication skills based on the COMSKIL CST program was established at the University of Leipzig. The goal of this course is to teach students about the kinds of communication scenarios they will encounter in their future working lives as care providers and equip them with the fundamental communication techniques and skills they need to successfully handle those situations. A formal evaluation of the program resulted in satisfactory findings, indicating that it is well suited for use in medical universities.

Antidepressant prescriptions and associated factors in men with prostate cancer and their female partners.

PURPOSE: To estimate the risk of first-time antidepressant prescriptions as a proxy for depression or anxiety and associated risk factors in patients with prostate cancer and their female partners. METHODS: We followed all men (n = 25,126) and their female cohabiting partners (n = 8785) without a history of cancer or antidepressants from the Danish Diet, Cancer and Health cohort from 1997 to 2014 or 2010, respectively. We estimated the cumulative incidence of first-time antidepressant prescriptions in men with prostate cancer compared with cancer-free men and their respective female partners, using the Danish National Prescription Registry. Sociodemographic, lifestyle-related, and clinical risk factors were assessed using Cox regression models. RESULTS: A total of 1828 men were diagnosed with prostate cancer of whom 15% received antidepressants. The unadjusted hazard ratio of antidepressant prescription was 2.18 (95%CI, 1.92, 2.48) for men with prostate cancer and 1.27 (95%CI, 0.87, 1.85) for their partners, compared with cancer-free men and their partners, respectively. After adjusting for sociodemographic, lifestyle-related, and comorbidity factors, this risk was 2-fold to 4-fold increased among patients, but not significantly increased among partners. Significant risk factors among patients were curative and palliative treatment (vs. active surveillance and watchful waiting), nonlocalized disease, and short education. CONCLUSIONS: Men with prostate cancer have a higher risk of receiving antidepressant medication than cancer-free men. Clinical characteristics can help clinicians in identifying patients at a high risk of depression or anxiety. IMPLICATIONS FOR CANCER SURVIVORS: Men with prostate cancer who experience symptoms of depression or anxiety should seek professional help early on. Patient education could aid in raising awareness and reducing the stigma associated with mental disorders.

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.

Frequency and network analysis of depressive symptoms in patients with cancer compared to the general population.

BACKGROUND: The use of sum scores of depressive symptoms has been increasingly criticized and may be particularly problematic in oncological settings. Frameworks analyzing individual symptoms and their interrelationships such as network analysis represent an emerging alternative. METHODS: We aimed to assess frequencies and interrelationships of 9 DSM-5 symptom criteria of major depression reported in the PHQ-9 questionnaire by 4020 patients with cancer and 4020 controls from the general population. We estimated unregularized Gaussian graphical models for both samples and compared network structures as well as predictability and centrality of individual symptoms. RESULTS: Depressive symptoms were more frequent, but less strongly intercorrelated in patients with cancer than in the general population. The overall network structure differed significantly between samples (correlation of adjacency matrices: rho=0.73, largest between-group difference in any edge weight: 0.20, p < 0.0001). Post-hoc tests showed significant differences in interrelationships for four symptom pairs. The mean variance of symptoms explained by all other symptoms in the same network was lower among cancer patients than in the general population (29% vs. 43%). LIMITATIONS: Cross-sectional data do not allow for temporal or causal inferences about the directions of associations and results from population-based samples may not apply to clinical psychiatric populations. CONCLUSIONS: In patients with cancer, both somatic and cognitive/affective depression symptoms are less likely to be explained by other depressive symptoms than in the general population. Rather than assuming a consistent depression construct, future research should study individual depressive symptom patterns and their potential causes in patients with cancer.

[Psychosocial Care For Patients With Amyotrophic Lateral Sclerosis: A Narrative Review]. / Psychosoziale Versorgung bei Patienten mit Amyotropher Lateralsklerose: Ein narrativer Review.

This narrative review gives a broad summary of the psychosocial strain in patients with amyotrophic lateral sclerosis (ALS) and psychotherapeutic interventions addressing these issues. ALS is a fatal, rapidly progressing neurodegenerative disease, which leads to weakness and atrophy in almost all muscles of the body, resulting in impairment and finally inability in all domains of daily life including mobility, food intake, respiration or communication. In addition to these mainly motor impairments, most patients are also affected by severe cognitive-emotional and behavioral alterations and deficits which may lead to additional distress. Due to the severe symptomatology and poor diagnosis, ALS can lead to significant psychosocial strain including heightened levels of depressive and anxious symptomatology, hopelessness and even the wish for hastened death. A large body of research demonstrates the strong effect of psychosocial aspects on quality of life (QoL) in ALS patients. Nevertheless, research on psychotherapeutic interventions for patients with ALS is very sparse to date. Besides the general lack of interventions and the methodological limitations in testing their efficacy, few of these therapeutic concepts incorporate the palliative character and the specific symptomatology of the disease such as impaired communication or problems with emotion control. Further research on psychosocial interventions in this patient group is therefore urgently needed. Future research could aim to adapt therapy programs that already have been proven to be effective in other populations with advanced diseases. Such research should also test the applicability of the therapy models using alternative communication including computer with a voice synthesizer or brain-computer-interfaces.

Educational level and the risk of depression after prostate cancer.

Background: The risk of depression is inversely associated with socioeconomic position in the general population; however, studies on the association in cancer populations are limited. The aim was to investigate if shorter education was associated with a higher risk of depression following prostate cancer diagnosis. Material and methods: This is a cohort study among participants in the Danish prospective Diet, Cancer and Health (DCH) study including 2337 men diagnosed with prostate cancer between 1997 and 2014. Primary outcome was indication of moderate to severe depression, defined as either a first hospital contact for depression or first use of antidepressants. The main indicator of socioeconomic position was education categorized into short (<9 years of education), medium (9-12 years) and long (>12 years). We retrieved information on education, depression and cohabitation status from Danish National Registries. Information on stage, primary treatment, lifestyle and anthropometry was obtained from medical records and questionnaires. Data were analyzed using Cox proportional hazards models adjusted for possible confounders and mediators. Results: The hazard of first depression was 1.86-fold higher (95% CI, 1.36-2.54) in prostate cancer patients with short education compared to those with long education. Adjustment for stage and primary treatment did not change the HRs, while adding comorbidity and lifestyle factors resulted in an HR of 1.65 (95% CI, 1.19-2.29). Men with medium education had a non-statistically significant 1.23-fold higher hazard of depression (95% CI, 0.95-1.59) than men with long education in the fully adjusted model. Educational differences were present in the cumulative incidence of first depression among cancer-free DCH study participants, but the level of first depression was substantially lower in this population than in prostate cancer patients. Conclusions: We found indication of social inequality in depression following prostate cancer. Patients and particularly men with short education might benefit from psychosocial intervention and support.

Return to Work in Patients with Hematological Cancers 1 Year after Treatment: A Prospective Longitudinal Study.

BACKGROUND: Although hematological cancer survivors have a high risk of disability, data on work-related issues are scarce for this population. METHODS: We investigated return to work (RTW) and work ability (Work Ability Index, WAI) in hematological cancer patients 6 months and 1 year after cancer treatment. We explored associations between baseline sociodemographic and medical characteristics and RTW as well as work ability at follow-up. RESULTS: The participation rate was 42% (baseline n = 91, after 12 months n = 40 (44%)). 6 months after cancer treatment, 33% (95% confidence interval 21%-46%) of the remaining patients had returned to work. After 12 months, the RTW rate was 58% (42%-73%). Mean WAI sum score ± SD significantly increased from 18.5 ± 7.3 at baseline to 28.3 ± 8.3 after 12 months (p = 0.001). Patients with lymphoma (r = 0.31, p = 0.02) and patients who received radiation therapy (r = 0.29, p = 0.04) were significantly more likely to return to work. Work ability after 6 months was most strongly associated with higher education (r = 0.60, p < 0.01). Patients' subjective prognosis of gainful employment before cancer treatment predicted work ability after 6 (r = 0.62, p < 0.01) and 12 months (r = 0.51, p < 0.01). CONCLUSION: The chance of returning to work of hematological malignancy survivors is similar to that of other cancer patients.

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.

COMSKIL Communication Training in Oncology-Adaptation to German Cancer Care Settings.

Medical communication is a skill which can be learned and taught and which can substantially improve treatment outcomes, especially if patients' communication preferences are taken into account. Here, we give an overview of communication training research and outline the COMSKIL program as a state-of-the-art communication skills training in oncology. COMSKIL has a solid theoretical foundation and teaches core elements of medical communication in up to ten fully operationalized modules. These address typical situations ranging from breaking bad news to responding to difficult emotions, shared decision-making, and communicating via interpreters.