Predictive Factors Associated with Declining Psycho-Oncological Support in Patients with Cancer.

(1) Background: International cancer treatment guidelines recommend low-threshold psycho-oncological support based on nurses' routine distress screening (e.g., via the distress thermometer and problem list). This study aims to explore factors which are associated with declining psycho-oncological support in order to increase nurses' efficiency in screening patients for psycho-oncological support needs. (2) Methods: Using machine learning, routinely recorded clinical data from 4064 patients was analyzed for predictors of patients declining psycho-oncological support. Cross validation and nested resampling were used to guard against model overfitting. (3) Results: The developed model detects patients who decline psycho-oncological support with a sensitivity of 89% (area under the cure of 79%, accuracy of 68.5%). Overall, older patients, patients with a lower score on the distress thermometer, fewer comorbidities, few physical problems, and those who do not feel sad, afraid, or worried refused psycho-oncological support. (4) Conclusions: Thus, current screening procedures seem worthy to be part of daily nursing routines in oncology, but nurses may need more time and training to rule out misconceptions of patients on psycho-oncological support.

GIP receptor agonism improves dyslipidemia and atherosclerosis independently of body weight loss in preclinical mouse model for cardio-metabolic disease.

BACKGROUND: Agonism at the receptor for the glucose-dependent insulinotropic polypeptide (GIPR) is a key component of the novel unimolecular GIPR:GLP-1R co-agonists, which are among the most promising drugs in clinical development for the treatment of obesity and type 2 diabetes. The therapeutic effect of chronic GIPR agonism to treat dyslipidemia and thus to reduce the cardiovascular disease risk independently of body weight loss has not been explored yet. METHODS: After 8 weeks on western diet, LDL receptor knockout (LDLR-/-) male mice were treated with daily subcutaneous injections of long-acting acylated GIP analog (acyl-GIP; 10nmol/kg body weight) for 28 days. Body weight, food intake, whole-body composition were monitored throughout the study. Fasting blood glucose and intraperitoneal glucose tolerance test (ipGTT) were determined on day 21 of the study. Circulating lipid levels, lipoprotein profiles and atherosclerotic lesion size was assessed at the end of the study. Acyl-GIP effects on fat depots were determined by histology and transcriptomics. RESULTS: Herein we found that treatment with acyl-GIP reduced dyslipidemia and atherogenesis in male LDLR-/- mice. Acyl-GIP administration resulted in smaller adipocytes within the inguinal fat depot and RNAseq analysis of the latter revealed that acyl-GIP may improve dyslipidemia by directly modulating lipid metabolism in this fat depot. CONCLUSIONS: This study identified an unanticipated efficacy of chronic GIPR agonism to improve dyslipidemia and cardiovascular disease independently of body weight loss, indicating that treatment with acyl-GIP may be a novel approach to alleviate cardiometabolic disease.

A short screening tool identifying systemic barriers to distress screening in cancer care.

INTRODUCTION: International guidelines on cancer treatment recommend screening for early detection and treatment of distress. However, screening rates are insufficient. In the present study, a survey was developed to assess perceived systemic barriers to distress screening. METHODS: A three-step approach was used for the study. Based on qualitative content analysis of interviews and an expert panel, an initial survey with 53 questions on barriers to screening was designed. It was completed by 98 nurses in a large comprehensive cancer center in Switzerland. From this, a short version of the survey with 24 questions was derived using exploratory principal component analysis. This survey was completed by 150 nurses in four cancer centers in Switzerland. A confirmatory factor analysis was then performed on the shortened version, yielding a final set of 14 questions. RESULTS: The initial set of 53 questions was reduced to a set of 14 validated questions retaining 53% of the original variance. These 14 questions allow for an assessment within 2-3 min that identifies relevant barriers to distress screening from the perspective of those responsible for implementation of distress screening. Across several hospitals in Switzerland, the timing of the first distress screening, lack of capacity, patient and staff overload, and refusal of distressed patients to be referred to support services emerged as major problems. CONCLUSION: The validated 14 questions on barriers to screening cancer patients for distress enable clinicians and hospital administrators to quickly identify relevant issues and take action to improve screening programs.

Clinically Significant Distress and Physical Problems Detected on a Distress Thermometer are Associated With Survival Among Lung Cancer Patients.

BACKGROUND: The distress thermometer is a well-established screening tool to detect clinically significant distress in cancer patients. It is often administered in combination with the problem list, differentiating further between various (e.g., physical and emotional) sources of distress. OBJECTIVE: The present study aimed to extend previous research on the association between distress and overall survival. A further exploratory analysis aimed to evaluate the predictive value of the problem list for overall survival. METHODS: Patients (n = 323) with newly diagnosed lung cancer were recruited from a large cancer center. Patients were split into 2 groups, those with (distress thermometer score ≥5) and those without significant distress. The overall survival time was illustrated by a Kaplan-Meier curve and compared with a log-rank test. Univariable Cox proportional hazard models were built to control the association of distress with overall survival for age, gender, disease stage, comorbidity, and their interaction terms. Multiple linear regression was used to investigate the association of the items from the problem list with survival time. RESULTS: Patients with significant distress had a shorter survival time than patients without significant distress (25 vs. 43 months). Regression analysis revealed more problems with both "bathing and dressing" and "eating," as well as absence of "diarrhea" and increased "nervousness," to negatively associated with the overall survival time. CONCLUSIONS: Our results show that estimation of the survival function using cancer-related distress is possible. However, when using Cox regression, distress shows no significant value for survival as a predictor. Moreover, our study did not reveal an interaction effect among disease stage, comorbidity, and distress. Overall, results suggest that physical and emotional problems that arise from lung cancer may be useful to identify patients at risk of poor prognosis (on the basis of Kaplan-Meier estimator).

Evaluation of distress management in inpatients with cancer by means of the distress thermometer: A mixed methods approach.

OBJECTIVES: To improve psychosocial care for oncology inpatients, we implemented screening for distress by means of distress thermometer (DT) at the Comprehensive Cancer Centre Zurich in 2011. Since then, several screening barriers have been reported regarding the application of the DT. This study aimed to evaluate the distress screening process between 2012 and 2016 to identify barriers preventing sustainability. METHODS: In this sequential explanatory mixed methods study, we synthesized the results of 2 quantitative retrospective descriptive studies and 1 qualitative focus group study. To compare and analyze the data, we used thematic triangulation. RESULTS: Nurses screened 32% (N = 7034) of all newly admitted inpatients with the DT, and 47% of the screenings showed a distress level ≥5. Of these cases, 9.7% were referred to psycho-oncological services and 44.7% to social services. In 15.7% of these cases, nurses generated a psychosocial nursing diagnosis. In focus group interviews, nurses attributed the low screening rate to the following barriers: adaptation to patients' individual needs, patient-related barriers and resistance, timing, communication challenges, established referral practice, and lack of integration in the nursing process. SIGNIFICANCE OF RESULTS: To improve distress screening performance, the screening process should be tailored to patients' needs and to nurses' working conditions (e.g., timing, knowledge, and setting-specific factors). To gain more evidence on distress management as a basis for practical improvements, further evaluations of distress screening are required.

Uncovering Barriers to Screening for Distress in Patients With Cancer via Machine Learning.

BACKGROUND: Psychologic distress and manifest mental disorders are overlooked in 30-50% of patients with cancer. Accordingly, international cancer treatment guidelines recommend routine screening for distress in order to provide psychologic support to those in need. Yet, institutional and patient-related factors continue to hinder implementation. OBJECTIVE: This study aims to investigate factors, which are associated with no screening for distress in patients with cancer. METHODS: Using machine learning, factors associated with lack of distress screening were explored in 6491 patients with cancer between 2011 and 2019 at a large cancer treatment center. Parameters were hierarchically ordered based on statistical relevance. Nested resampling and cross validation were performed to avoid overfitting and to comply with assumptions for machine learning approaches. RESULTS: Patients unlikely to be screened were not discussed at a tumor board, had inpatient treatment of less than 28 days, did not consult with a psychiatrist or clinical psychologist, had no (primary) nervous system cancer, no head and neck cancer, and did have breast or skin cancer. The final validated model was optimized to maximize sensitivity at 83.9%, and achieved a balanced accuracy of 68.9, area under the curve of 0.80, and specificity of 53.9%. CONCLUSION: Findings of this study may be relevant to stakeholders at both a clinical and institutional level in order to optimize distress screening rates.

Wie erleben und beurteilen Pflegende das Screening von stationären onkologischen Patient_innen mit dem Belastungsthermometer?

How do nurses experience and interpret the screening of hospitalised cancer patients by means of the distress thermometer? - A qualitative study Abstract. Background: People with cancer experience distress and may need professional support. In 2012, the University Hospital Zurich introduced its distress thermometer (DT) screening, whereby all inpatients were to be screened to gauge their support need. However, after five years, the screening rate was 40 % and the referral rate to psycho oncology was 7.9 %, surprisingly low. Aim: The aim of this qualitative study was to describe how nurses experience the screening and how they interpret the screening and referral rate. Methods: The evaluation of three focus group interviews with 14 nurses followed the principles of qualitative content analysis according to Mayring. Results: The analysis revealed four main categories. The first category "Trying to perform useful screening in a complex daily routine" comprises three subcategories: "Using the benefits of screening for comprehensive care", "The best way to recognize the individuality of the counterpart" and "Failing due to structural and personal barriers". Three further main categories addressing nurses' personal attitudes complete the screening experience: "Experiencing fewer difficulties due to competence and experience", "Being careful due to hesitations", and "Reflecting one's responsibility". Conclusions: Nurses want to use the DT. However, they need more practical and scientific support to usefully integrate screening into their everyday life.

Adherence to the distress screening through oncology nurses and integration of screening results into the nursing process to adapt psychosocial nursing care five years after implementation.

PURPOSE: Addressing psychosocial distress is an essential part of cancer care. Therefore, nurses at the University Hospital Zurich have been screening all cancer inpatients with the Distress Thermometer (DT) since 2012. Screening is ineffective without any form of psychosocial intervention. We aimed to identify adherence to the screening protocol and how the reported problems influenced the nursing process. We compared changes in the documentation before and after screening implementation. METHODS: This retrospective descriptive study used screening data and documentation of psychosocial items in the nursing process of inpatients at an oncologic ward. These data were compared with data obtained before screening implementation and were collected from electronic health records. All data were analyzed descriptively. RESULTS: 65% (N = 1111) of the 2166 inpatients were screened. With the implementation, more psycho-oncological referrals were made (4.5% vs. 11.7%) and more psychosocial issues were described in the nursing process (24.6% vs. 51.2%). Inpatients mentioned emotional problems in 37.5% (N = 353) and physical problems in 47.4% (N = 504) of cases. 15.7% (147) had a psychosocial nursing diagnosis. Only 10.7% (N = 26) of patients who noted anxiety, also had a nursing diagnosis of "anxiety". In contrast, 71.1% (N = 202) of patients who noted pain, had a nursing diagnosis of "pain". CONCLUSIONS: Although nurses are more sensitised to psychosocial issues after DT implementation, they do not use screening results to adapt nursing documentation to the psychosocial needs of the patients. Further studies are needed to investigate how distress screening and psychosocial issues can be integrated into nurses' daily work.

Evaluation of the adherence of distress screening with the distress thermometer in cancer patients 4 years after implementation.

PURPOSE: Identifying and assessing psychosocial distress with an appropriate screening instrument is essential when caring for cancer patients. Since 2012, the distress thermometer (DT) has been used by nurses for all cancer inpatients at the Comprehensive Cancer Center Zurich. We wanted to identify nurses' adherence to the screening protocol, differences between screened and not screened patients and the relationship between screening rate and productivity. METHODS: This retrospective descriptive study used screening and referral data as well as socioeconomic and disease-related data of inpatients at the Comprehensive Cancer Center Zurich. This was collected from the electronic patient documentation system. Additionally, data showing the productivity of all wards was used. All data were analyzed descriptive. RESULTS: Since 2012, 40.6% (4541) of the 11,184 patients have been screened. The screening rate was initially significantly lower but settled at 40% after 2 years. There was a higher screening rate among Swiss, married, male, and emergency patients and patients with hematology diseases, brain tumors, or head and neck cancer (p < 0.001). Every fourth patient with a moderate to severe distress level requested referral to a psychosocial service. Significantly more screened patients were referred to the social service (44.7%) than to the psycho-oncology service (9.4%). Only 22.9% of all referrals were made on the day of screening or a day later. There were only two wards of 15 with a significant relationship between productivity and screening rate. CONCLUSIONS: Screening is useful in recognizing distress among patients, but screening practice needs to be reconsidered.

Circulating HDL levels control hypothalamic astrogliosis via apoA-I.

Meta-inflammation of hypothalamic areas governing energy homeostasis has recently emerged as a process of potential pathophysiological relevance for the development of obesity and its metabolic sequelae. The current model suggests that diet-induced neuronal injury triggers microgliosis and astrocytosis, conditions which ultimately may induce functional impairment of hypothalamic circuits governing feeding behavior, systemic metabolism, and body weight. Epidemiological data indicate that low circulating HDL levels, besides conveying cardiovascular risk, also correlate strongly with obesity. We simulated that condition by using a genetic loss of function mouse model (apoA-I-/-) with markedly reduced HDL levels to investigate whether HDL may directly modulate hypothalamic inflammation. Astrogliosis was significantly enhanced in the hypothalami of apoA-I-/- compared with apoA-I+/+ mice and was associated with compromised mitochondrial function. apoA-I-/- mice exhibited key components of metabolic disease, like increased fat mass, fasting glucose levels, hepatic triglyceride content, and hepatic glucose output compared with apoA-I+/+ controls. Administration of reconstituted HDL (CSL-111) normalized hypothalamic inflammation and mitochondrial function markers in apoA-I-/- mice. Treatment of primary astrocytes with apoA-I resulted in enhanced mitochondrial activity, implying that circulating HDL levels are likely important for astrocyte function. HDL-based therapies may consequently avert reactive gliosis in hypothalamic astrocytes by improving mitochondrial bioenergetics and thereby offering potential treatment and prevention for obesity and metabolic disease.

Metabolic syndrome and extensive adipose tissue inflammation in morbidly obese Göttingen minipigs.

OBJECTIVE: The worldwide prevalence of obesity has increased to 10% in men and 15% in women and is associated with severe comorbidities such as diabetes, cancer, and cardiovascular disease. Animal models of obesity are central to experimental studies of disease mechanisms and therapeutic strategies. Diet-induced obesity (DIO) models in rodents have provided important insights into the pathophysiology of obesity and, in most instances, are the first in line for exploratory pharmacology studies. To deepen the relevance towards translation to human patients, we established a corresponding DIO model in Göttingen minipigs (GM). METHODS: Young adult female ovariectomized GM were fed a high-fat/high-energy diet for a period of 70 weeks. The ration was calculated to meet the requirements and maintain body weight (BW) of lean adult minipigs (L-GM group) or increased stepwise to achieve an obese state (DIO-GM group). Body composition, blood parameters and intravenous glucose tolerance were determined at regular intervals. A pilot chronic treatment trial with a GLP1 receptor agonist was conducted in DIO-GM. At the end of the study, the animals were necropsied and a biobank of selected tissues was established. RESULTS: DIO-GM developed severe subcutaneous and visceral adiposity (body fat >50% of body mass vs. 22% in L-GM), increased plasma cholesterol, triglyceride, and free fatty acid levels, insulin resistance (HOMA-IR >5 vs. 2 in L-GM), impaired glucose tolerance and increased heart rate when resting and active. However, fasting glucose concentrations stayed within normal range throughout the study. Treatment with a long-acting GLP1 receptor agonist revealed substantial reduction of food intake and body weight within four weeks, with increased drug sensitivity relative to observations in other DIO animal models. Extensive adipose tissue inflammation and adipocyte necrosis was observed in visceral, but not subcutaneous, adipose tissue of DIO-GM. CONCLUSIONS: The Munich DIO-GM model resembles hallmarks of the human metabolic syndrome with extensive adipose tissue inflammation and adipocyte necrosis reported for the first time. DIO-GM may be used for evaluating novel treatments of obesity and associated comorbidities. They may help to identify triggers and mechanisms of fat tissue inflammation and mechanisms preventing complete metabolic decompensation despite morbid obesity.

Gut hormone polyagonists for the treatment of type 2 diabetes.

Chemical derivatives of the gut-derived peptide hormone glucagon-like peptide 1 (GLP-1) are among the best-in-class pharmacotherapies to treat obesity and type 2 diabetes. However, GLP-1 analogs have modest weight lowering capacity, in the range of 5-10%, and the therapeutic window is hampered by dose-dependent side effects. Over the last few years, a new concept has emerged: combining the beneficial effects of several key metabolic hormones into a single molecular entity. Several unimolecular GLP-1-based polyagonists have shown superior metabolic action compared to GLP-1 monotherapies. In this review article, we highlight the history of polyagonists targeting the receptors for GLP-1, GIP and glucagon, and discuss recent progress in expanding of this concept to now allow targeted delivery of nuclear hormones via GLP-1 and other gut hormones, as a novel approach towards more personalized pharmacotherapies.

Introduction of the distress thermometer on an oncological ward / Einführung des Belastungsthermometers auf einer onkologischen Station.

Background: Patients suffering from oncological diseases experience physical, mental, social, and spiritual distress. 20 to 40 % show increased stress and need professional support. Therefore, we implemented the distress thermometer (DT) as a screening instrument on an inpatient oncological ward. Method: We chose an action research approach ("look"-"think"-"act"-cycle) for this practice development project. Firstly, we examined the current assessment of psychosocial distress and conducted a literature research ("look"). On this basis we elaborated an instruction for the DT ("think") and implemented the instrument ("act"). We evaluated the project by analyzing the completed DT questionnaires and by conducting a survey of patients and nurses ("look"). Results: After implementing the DT, mentions of psychosocial distress in patient records increased by 40 %. Before the implementation, distress was documented in only 39.5 % of patient records and 4.5 % of all patients were referred to the psycho-oncology service. After introducing the DT, psychosocial stress was mentioned in 86 % of patient records and 7.3 % of patients received psycho-oncological counselling. 49.6 % of patients were screened. Nurses considered the screening tool as useful and supportive. Conclusions: By means of the DT, a systematic screening of psychosocial distress is feasible. The instrument can be easily implemented and applied in daily practice.