Work after mental-health-related absence: a qualitative study of perceived change after a combination of metacognitive therapy and work-focused interventions.

BACKGROUND: Sick leave caused by common mental health disorders (CMD) is becoming more prevalent. For most people, work is essential for good mental and physical health. It is necessary to provide treatments that facilitate return to work (RTW) and a reduction of symptoms. A qualitative study can contribute to an understanding of what makes an intervention successful. The aim of this study was to investigate how individuals who are on sick leave because of CMD perceive and handle their symptoms and their work, after completing metacognitive therapy and work-focused interventions. METHODS: Semi-structured interviews were conducted with 23 participants after they had completed therapy. Thematic analysis was used to analyse the data. RESULTS: Through both therapy and the process of RTW, the participants had gained increased awareness and understanding of their mental health problems and the relationship between those problems and work. Together with the sense that they were in charge of their own process of RTW, this helped to improve their self-confidence. An important part of the process was the change to new strategies and the rejection of older maladaptive ones, in relation to both mental health and work. Being open about their mental illness in the workplace could lead to support but also to the opposite, and therefore not an option for everyone. After treatment, most had returned to work and gained a more positive outlook on the future, but some had less confidence in their ability to deal with future symptoms and workplace issues. CONCLUSIONS: Achieving improved self-confidence and adopting new strategies, which enabled them to change how they related to their mental problems and how they addressed their problems at work, seemed to have increased their self-efficacy. Active involvement in therapy and at work was also important, both for the process and as a way of increasing self-efficacy. This gave them renewed belief in themselves and in their ability to handle their work at present and in the future. Despite this being a manualized treatment, the participants' experience was that it was adapted to each individual, something they regarded as important.

Screening for symptoms of depression and anxiety in a cardiology department. / Screening for symptomer på depresjon og angst ved en hjertemedisinsk avdeling.

BACKGROUND: Depression and anxiety are common in patients with cardiac disease and predict a poorer prognosis, increased mortality and reduced compliance with treatment. National and international guidelines recommend procedures for screening, but there is a lack of studies of such practices in Norwegian hospitals. The objective of this study was to implement a simple screening method for symptoms of depression and anxiety in patients with cardiac disease. MATERIAL AND METHOD: Patients in the Department of Cardiology at Diakonhjemmet Hospital who had valvular heart disease, tachyarrhythmia, myocardial infarction or heart failure were screened for symptoms of depression, anxiety and panic attacks with the aid of five questions from the Patient Health Questionnaire-2 (PHQ-2), Generalized Anxiety Disorder Scale-2 (GAD-2) and Patient Health Questionnaire - Somatic, Anxiety, and Depressive Symptom Scales (PHQ-SADS). The patients were recruited from the outpatient clinic or ward at least one month after acute heart disease. RESULTS: A total of 57 of 232 patients reported symptoms of depression or anxiety when screened. The screening method was easy to implement, but time constraints and uncertainty regarding procedures for follow-up and the effect of following up the patients were reported. INTERPRETATION: Good tools and methods are available for screening for symptoms of depression and anxiety and anxiety in patients with cardiac disease. More studies are needed regarding the benefits of screening, at what stage of the disease it should be performed, and whether it should be performed by the primary and/or the specialist health services.

Photochemical activation of MH3-B1/rGel: a HER2-targeted treatment approach for ovarian cancer.

HER2-targeted therapy has been shown to have limited efficacy in ovarian cancer despite frequent overexpression of this receptor. Photochemical internalization (PCI) is a modality for cytosolic drug delivery, currently undergoing clinical evaluation. In the present project we studied the application of PCI in combination with the HER2-targeted recombinant fusion toxin, MH3-B1/rGel, for the treatment of ovarian cancer. The SKOV-3 cell line, resistant to trastuzumab- and MH3-B1/rGel- monotherapy, was shown to respond strongly to PCI of MH3-B1/rGel to a similar extent as observed for the treatment-sensitive SK-BR-3 breast cancer cells. Extensive hydrolytic degradation of MH3-B1/rGel in acidic endocytic vesicles was indicated as the mechanism of MH3-B1/rGel resistance in SKOV-3 cells. This was shown by the positive Pearson's correlation coefficient between Alexa488-labeled MH3-B1/rGel and Lysotracker in SKOV-3 cells in contrast to the negative Pearson's correlation coefficient in SK-BR-3 cells. The application of PCI to induce the release of MH3-B1/rGel was also demonstrated to be effective on SKOV-3 xenografts. Application of PCI with MH3-B1/rGel was further found highly effective in the HER2 expressing HOC-7 and NuTu-19 ovarian cancer cell lines. The presented results warrant future development of PCI in combination with MH3-B1/rGel as a novel therapeutic approach in preclinical models of ovarian cancer.

Photochemical activation of drugs for the treatment of therapy-resistant cancers.

Resistance to chemotherapy, molecular targeted therapy as well as radiation therapy is a major obstacle for cancer treatment. Cancer resistance may be exerted through multiple different mechanisms which may be orchestrated as observed in multidrug resistance (MDR). Cancer resistance may be intrinsic or acquired and often leaves patients without any treatment options. Strategies for alternative treatment modalities for resistant cancer are therefore highly warranted. Photochemical internalization (PCI) is a technology for cytosolic delivery of macromolecular therapeutics based on the principles of photodynamic therapy (PDT). The present report reviews the current knowledge of PCI of therapy-resistant cancers. In summary, PCI may be able to circumvent several of the major mechanisms associated with resistance towards chemotherapeutics including increased expression of drug efflux pumps, altered intracellular drug distribution and increased ROS scavenging. Current data also suggest PCI of targeted toxins as highly effective in cancers resistant to clinically available targeted therapy such as monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs). PCI may therefore, in general, represent a future treatment option for cancers resistant to other therapies.

Photochemical activation of the recombinant HER2-targeted fusion toxin MH3-B1/rGel; Impact of HER2 expression on treatment outcome.

HER2 is overexpressed in 20-30% of breast tumors and is associated with aggressiveness and increased risk of recurrence and death. The HER2 protein is internalized as a part of its activity, and may therefore be utilized as a target for the specific intracellular delivery of drugs. Photochemical internalization (PCI) is a novel technology now undergoing clinical evaluation for its ability to improve the release into the cytosol of drugs entrapped in the endo/lysosomal compartment. PCI employs an amphiphilic photosensitizer which localizes in the membranes of endo/lysosomes. Subsequent light exposure (visible light) causes destabilization of the endo/lysosomal membranes. PCI has been proven highly effective for improving the cytosolic delivery of targeted toxins based on type I ribosome inactivating protein toxins such as gelonin. We examined the impact of the level of target antigen expression on PCI efficacy. Four human breast cancer cell lines (MDA-MB-231, BT-20, Zr-75-1 and SK-BR-3) covering a wide range of HER2 expression were included in the present study. PCI of the HER2-targeted fusion toxin MH3-B1/rGel was found to be highly effective in all four cell lines. The increase in PCI-mediated efficacy was not directly correlated with the cellular levels of HER2 as assessed by western blots, the overall uptake of MH3-B1/rGel as measured by flow cytometry, the amount of MH3-B1/rGel localized to endo/lysosomes assessed by confocal microscopy or the cell sensitivity to the photochemical treatment itself (photosensitizer and light without MH3-B1/rGel). However, correcting the PCI efficacy for the baseline cellular sensitivity to rGel revealed a linear correlation (R(2)=0.80) with HER2 expression. The present report therefore concludes the cellular sensitivity to the toxin as an important parameter for PCI efficacy and also indicates PCI of a HER2-targeted fusion toxin as an attractive treatment alternative for breast cancer patients with both HER2-low and -high expression.