Excess body weight and postmenopausal breast cancer: Emerging molecular mechanisms and perspectives.

Postmenopausal, obese women have a significantly higher risk of developing estrogen receptor-positive (ER+) breast tumors, that are resistant to therapies and are associated with higher recurrence and death rates. The global prevalence of overweight/obese women has reached alarming proportions and with postmenopausal ER+ breast carcinoma (BC) having the highest incidence among the three obesity-related cancers in females (i.e., breast, endometrial and ovarian), this is of significant concern. Elucidation of the precise molecular mechanisms underlying the pro-cancerous action of obesity in ER+BC is therefore critical for disease prevention and novel treatment initiatives. Interestingly, accumulating data has shown opposing relationships between obesity and cancer in either pre- or post-menopausal women. Excess body weight is associated with an increased risk of breast cancer in postmenopausal women and a decreased risk in pre-menopausal women. Moreover, excess adiposity during early life appears to be protective against postmenopausal breast cancer, including both ER+ and ER negative BC subtypes. Overall, estrogen-dependent mechanisms have been implicated as the main driving force in obesity-related breast tumorigenesis. In the present review we discuss the epidemiologic and mechanistic aspects of association between obesity and breast tumors after menopause, mainly in the context of hormone dependency. Molecular and cellular events underlying this association present as potential avenues for both therapeutic intervention as well as the prevention of BC-promoting processes linked to excess adiposity, which is proving to be vital in an increasingly obese global population.

The cost-utility of a return-to-work intervention in comparison to routine care for patients with mental disorders in Germany: Results from the RETURN project.

BACKGROUND: Only two-thirds of patients admitted to psychiatric wards return to their previous jobs. Return-to-work interventions in Germany are investigated for their effectiveness, but information regarding cost-effectiveness is lacking. This study investigates the cost-utility of a return-to-work intervention for patients with mental disorders compared to treatment as usual (TAU). METHODS: We used data from a cluster-randomised controlled trial including 166 patients from 28 inpatient psychiatric wards providing data at 6- and 12-month follow-ups. Health and social care service use was measured with the Client Sociodemographic and Service Receipt Inventory. Quality of life was measured with the EQ-5D-3L questionnaire. Cost-utility analysis was performed by calculating additional costs per one additional QALY (Quality-Adjusted Life Years) gained by receiving the support of return-to-work experts, in comparison to TAU. RESULTS: No significant cost or QALY difference between the intervention and control groups has been detected. The return-to-work intervention cannot be identified as cost-effective in comparison to TAU. CONCLUSIONS: The employment of return-to-work experts could not reach the threshold of providing good value for money. TAU, therefore, seems to be sufficient support for the target group.

[Return-to-Work - The Transition after Psychiatric Inpatient Treatment]. / Return-to-Work ­ Übergangsprozesse nach Behandlung in einem psychiatrischen Akutkrankenhaus.

OBJECTIVES: Workers on sick-leave due to a mental illness have enormous problems to return to work. The main objective of the present study is to examine, how individuals experience the transition from the mental health system to their workplace. METHODS: A qualitative research design guided by a grounded theory approach was used. Narrative interviews with ten workers on sick leave and four semi-structured interviews with return-to-work-experts were conducted. RESULTS: Relevant for returning to work is the interplay between the involved persons. Essential is the interpretation of the transition and as a result, which calls for action are made to the participants. CONCLUSION: Clinical interventions for returning to work should focus the support on the expectations of the participants and stimulate a common interpretation.

Supporting return to work after psychiatric hospitalization-A cluster randomized study (RETURN-study).

BACKGROUND: If people with episodic mental-health conditions lose their job due to an episode of their mental illness, they often experience personal negative consequences. Therefore, reintegration after sick leave is critical to avoid unfavorable courses of disease, longer inability to work, long payment of sickness benefits, and unemployment. Existing return-to-work (RTW) programs have mainly focused on "common mental disorders" and often used very elaborate and costly interventions without yielding convincing effects. It was the aim of the RETURN study to evaluate an easy-to-implement RTW intervention specifically addressing persons with mental illnesses being so severe that they require inpatient treatment. METHODS: The RETURN study was a multi-center, cluster-randomized controlled trial in acute psychiatric wards addressing inpatients suffering from a psychiatric disorder. In intervention wards, case managers (RTW experts) were introduced who supported patients in their RTW process, while in control wards treatment, as usual, was continued. RESULTS: A total of 268 patients were recruited for the trial. Patients in the intervention group had more often returned to their workplace at 6 and 12 months, which was also mirrored in more days at work. These group differences were statistically significant at 6 months. However, for the main outcome (days at work at 12 months), differences were no longer statistically significant (p = 0.14). Intervention patients returned to their workplace earlier than patients in the control group (p = 0.040). CONCLUSIONS: The RETURN intervention has shown the potential of case-management interventions when addressing RTW. Further analyses, especially the qualitative ones, may help to better understand limitations and potential areas for improvement.

How do employees currently admitted to acute psychiatric inpatient units rate their psychosocial working conditions with the COPSOQ (Copenhagen Psychosocial Questionnaire).

BACKGROUND: In recent years it could be shown that psychosocial working conditions and mental health of employees are closely correlated. One well-established instrument to measure psychosocial stress at work is the COPSOQ (Copenhagen Psychosocial Questionnaire, German Standard Version). It is an 84 item self-rating instrument addressing several domains of psychosocial working conditions and is generally used for risk assessments in companies. AIMS: To examine associations between COPSOQ ratings with clinical features and symptoms of employees who currently suffer from an episode of a mental illness requiring inpatient treatment. METHOD: For 265 inpatients with mental disorders who participated in a cluster randomized trial (RETURN-study) COPSOQ-data were available as part of the baseline data acquisition. These data were compared with the German COPSOQ validation sample of the Freiburg research center for occupational sciences (FFAW; approximately 250,000 participants). For subdomains of the COPSOQ that showed major and significant differences between the two samples regression analyses were done to predict COPSOQ scores within the RETURN-sample. RESULTS: Psychiatric inpatients did not assess their working conditions significantly different compared to the population based FFAW sample. However, with regard to the effects of working conditions (general health, burnout, presenteeism, and intention to leave the job) there were major differences between the two samples with the clinical sample expressing more negative views. In the RETURN sample these were predicted by a greater expression of depressive symptoms. CONCLUSIONS: The linkage between work and mental wellbeing is complex. Mental illness is not necessarily a result of poor working conditions, while good working conditions may not in every case prevent symptoms of bad health, even if such associations exist.

[Development of a Return-to-work Intervention for Psychiatric Inpatients]. / Entwicklung einer Intervention zur Unterstützung von stationär-psychiatrisch behandelten Patienten bei der Rückkehr an den Arbeitsplatz im Rahmen der RETURN-Studie.

OBJECTIVE: Patients with mental illnesses often face difficulties when returning to workplace after an episode of inpatient treatment. Available resources intended to support the return-to-work process are often not used. It was the aim of the present study to develop an intervention that facilitates the implementation of patient support at the interface of in- and outpatient care. METHODS: We used a structured development process for the establishment of a return-to-work intervention for psychiatric inpatients. RESULTS: The intervention consisted of the use of return-to-work experts who worked on the basis of a manual. In clearly defined modules, patients were given information on social law basics and details of the return process. Difficult situations (e. g., dealing with the disclosure of the diagnosis, return interview) were discussed and rehearsed. After discharge, further care took place, above all with regard to experiences on the first working day, accompaniment to discussions with the employer and support with any other upcoming difficulties. CONCLUSION: The results of the ongoing study will show whether the chosen approach actually yields the expected results, namely an improvement of the return-to-work process.

Macrophages Upregulate Estrogen Receptor Expression in the Model of Obesity-Associated Breast Carcinoma.

Breast cancer (BC) and obesity are two heterogeneous conditions with a tremendous impact on health. BC is the most commonly diagnosed neoplasm and the leading cause of cancer-related mortality among women, and the prevalence of obesity in women worldwide reaches pandemic proportions. Obesity is a significant risk factor for both incidence and worse prognosis in estrogen receptor positive (ER+) BC. Yet, the mechanisms underlying the association between excess adiposity and increased risk/therapy resistance/poorer outcome of ER+, but not ER-negative (ER-), BC are not fully understood. Tumor-promoting action of obesity, predominantly in ER + BC patients, is often attributed to the augmented production of estrogen in 'obese' adipose tissue. However, in addition to the estrogen production, expression levels of ER represent a key determinant in hormone-driven breast tumorigenesis and therapy response. Here, utilizing in vitro and in vivo models of BC, we show that macrophages, whose adverse activation by obesogenic substances is fueled by heparanase (extracellular matrix-degrading enzyme), are capable of upregulating ER expression in tumor cells, in the setting of obesity-associated BC. These findings underscore a previously unknown mechanism through which interplay between cellular/extracellular elements of obesity-associated BC microenvironment influences estrogen sensitivity-a critical component in hormone-related cancer progression and resistance to therapy.

Mental Health Surveillance at federal state level - Reporting on psychiatry in Bavaria.

In Germany, mental health reporting is organised at the federal, federal state and municipal level. At federal level, a number of concepts and approaches are implemented. In 2020 and 2021, in accordance with Article 4 of the Mental Health Assistance Act the first Bavarian Psychiatry Report was prepared. Important data bases include the billing and care data of Bavaria's Association of Statutory Health Insurance Physicians and the administrative data of the Bavarian districts. The aim is to enhance coordination between these federal state projects and Mental Health Surveillance at national level, in particular regarding the use of health care data.

[Return to Work after Mental Disorders - A Scoping Review]. / Rückkehr an den Arbeitsplatz nach psychischer Erkrankung ­ Ein Scoping Review.

OBJECTIVE: Workers on sick-leave due to a mental disorder have enormous problems to return to work. The main objective of this review is to examine different return-to-work (RTW) interventions. METHODS: We conduct a systematic literature research. RESULTS: 88 articles were screened and 29 studies included. The included RTW-interventions build on different approaches: 1) individual, 2) workplace, 3) mental health services. The majority of the interventions showed positive effects on the return-to-work process. CONCLUSION: Even if not all interventions could be readily transferred to the German context, the findings indicate ways improving the transition from the mental health system to the workplace.

Return-to-work-experts for inpatient treatment of patients with mental illnesses- a proof-of-concept-study (RETURN): the study protocol.

BACKGROUND: Patients with mental illnesses often have massive difficulties returning to work after inpatient treatment at a psychiatric clinic and are often at risk of losing their jobs. The psychosocial support for this patient group at the interface of clinic/outpatient care is often insufficient. METHODS/DESIGN: The RETURN-study prospectively assesses and surveys 200 patients with mental disorders in a cluster randomized intervention study, i.e. treatment teams and patients from intervention wards receive a return-to-work (RTW) intervention. Patients in control wards obtain treatment as usual (TAU). Pairs of comparable wards (similar patient population, similar staff density) have been identified and then randomized for control and intervention (n = 14 for each condition). On intervention wards return-to-work experts (RTW experts) who focus treatment on the workplace-related needs of patients with mental illnesses have been established. These RTW experts ensure the use of available resources within the framework of work-related discharge management and should lead to a more successful return to the workplace. The days at work in the year after release will be evaluated in a mixed methods approach as well as the return rate in the year after release, disability days in the year after return, relapse rate after 12 months, cost-benefit ratio of the intervention, analysis of the predictors / barriers for a successful return to the workplace (e.g. psychopathology, cognition, stigma, social-psychiatric support, company support, etc.), possibilities to implement the concept of RTW experts in standard psychiatric care (TAU - treatment as usual), the impact of the RTW experts' approach on the treatment process in standard psychiatric care. DISCUSSION: This approach is already internationally established in the field of somatic rehabilitation and supported employment [Am J Psychiatry 171:1183-90, 2014; Lancet 370:1146-52, 2007; Cochrane Database Syst Rev, doi:10.1002/14651858.CD006237.pub3, 2014]; the innovative aspect of this project is to implement and evaluate it in standard psychiatric care in Germany. This project requires no new interventions to be developed and tested, as the techniques of the case manager/job coach is applied to the field of return to work. TRIAL REGISTRATION: The study was registered in Deutsches Register Klinische Studien searchable via its Meta-registry (http://apps.who.int/trialsearch/), Trial registration number: DRKS00016037, Date of registration: 21/12/2018, URL of trial registry record.

Female mice are more susceptible to nonalcoholic fatty liver disease: sex-specific regulation of the hepatic AMP-activated protein kinase-plasminogen activator inhibitor 1 cascade, but not the hepatic endotoxin response.

As significant differences between sexes were found in the susceptibility to alcoholic liver disease in human and animal models, it was the aim of the present study to investigate whether female mice also are more susceptible to the development of non-alcoholic fatty liver disease (NAFLD). Male and female C57BL/6J mice were fed either water or 30% fructose solution ad libitum for 16 wks. Liver damage was evaluated by histological scoring. Portal endotoxin levels and markers of Kupffer cell activation and insulin resistance, plasminogen activator inhibitor 1 (PAI-1) and phosphorylated adenosine monophosphate-activated protein kinase (pAMPK ) were measured in the liver. Adiponectin mRNA expression was determined in adipose tissue. Hepatic steatosis was almost similar between male and female mice; however, inflammation was markedly more pronounced in livers of female mice. Portal endotoxin levels, hepatic levels of myeloid differentiation primary response gene (88) (MyD88) protein and of 4-hydroxynonenal protein adducts were elevated in animals with NAFLD regardless of sex. Expression of insulin receptor substrate 1 and 2 was decreased to a similar extent in livers of male and female mice with NAFLD. The less pronounced susceptibility to liver damage in male mice was associated with a superinduction of hepatic pAMPK in these mice whereas, in livers of female mice with NAFLD, PAI-1 was markedly induced. Expression of adiponectin in visceral fat was significantly lower in female mice with NAFLD but unchanged in male mice compared with respective controls. In conclusion, our data suggest that the sex-specific differences in the susceptibility to NAFLD are associated with differences in the regulation of the adiponectin-AMPK-PAI-1 signaling cascade.