Group and individual change in cognitive functioning in patients with 1 to 10 brain metastases following Gamma Knife radiosurgery

Aims:  Stereotactic radiosurgery is increasingly used to treat multiple (four or more) brain metastases. Preserving cognitive functions is a highly relevant treatment goal because cognitive deteriorations may negatively affect a patient's quality of life. The aim of this study was to assess cognitive change, at the group and individual level, in patients with 1 to 10 brain metastases up to 9 months after Gamma Knife radiosurgery (GKRS). Materials and methods:  Ninety-two patients with 1 to 10 newly diagnosed brain metastases, expected survival >3 months and Karnofsky Performance Status (KPS) ≥70 and 104 non-cancer controls were included. A neuropsychological test battery was administered before GKRS (n = 92) and at 3 (n = 66), 6 (n = 52) and 9 (n = 41) months after GKRS. The course of test performances, while taking into account practice effects, was analysed using linear mixed models. Pre-GKRS predictors of cognitive trajectories were analysed. To determine proportions of individuals with cognitive changes, reliable change indices, with correction for practice effects, were calculated. Results:  At the group level, immediate memory, working memory and information processing speed significantly improved over 9 months after GKRS. There were no cognitive declines. Neither number nor volume of brain metastases influenced cognitive change over time. At the individual level, proportions of patients with stable, improved or declined performances were comparable with controls, except for information processing speed (more individuals with improvements in patients) and motor dexterity (more improvements and declines in patients). Conclusions:  Cognitive functioning in patients with 1 to 10 brain metastases was preserved, or improved, up to 9 months after GKRS. Neither number nor volume of brain metastases influenced cognitive performance

Multidimensional assessment of fatigue in patients with brain metastases before and after Gamma Knife radiosurgery

Purpose  Fatigue is a common and distressing symptom in cancer patients which negatively affects patients' daily functioning and health-related quality of life. The aim of this study was to assess multidimensional fatigue in patients with brain metastases (BM) before, and after Gamma Knife radiosurgery (GKRS).  Methods  Patients with BM, an expected survival > 3 months, and a Karnofsky Performance Status >= 70 and 104 Dutch non-cancer controls were recruited. The Multidimensional Fatigue Inventory (MFI), measuring general fatigue, physical fatigue, mental fatigue, reduced activity and reduced motivation, was used. Baseline levels of fatigue between patients and controls were compared using independent-samples t-tests. The course of fatigue over time, and clinical and psychological predictors thereof, were analyzed using linear mixed models (within-group analyses).  Results  Ninety-two, 67 and 53 patients completed the MFI at baseline, and 3 and 6 months after GKRS. Before GKRS, patients with BM experienced significantly higher levels of fatigue on all subscales compared to controls (medium to large effect sizes). Over 6 months, general and physical fatigue increased significantly (p = .009 and p <.001), and levels of mental fatigue decreased significantly (p = .027). No significant predictors of the course of fatigue over time could be identified.  Conclusions  Fatigue is a major problem for patients with BM. Different patterns over time were observed for the various aspects of fatigue in patients with BM. Information on the various aspects of fatigue is important because fatigue may negatively affect patients' functional independence, health-related quality of life, and adherence to therapy

Determinants and consequences of polypharmacy in patients with a depressive disorder in later life

OBJECTIVES: Polypharmacy and late-life depression often congregate in the geriatric population. The primary objective is to identify determinants of polypharmacy in patients with depression, and second to examine polypharmacy in relation to various clinical phenotypes of depression and its course. METHODS: A longitudinal observational study using data of the Netherlands Study of Depression in Older persons (NESDO) including 375 patients with depression ≥ 60 years and 132 non-depressed comparisons. Linear and logistic regression were used to analyze both polypharmacy (dichotomous: ≥ 5 medications) and number of prescribed drugs (continuous) in relation to depression, various clinical phenotypes, and depression course. RESULTS: Polypharmacy was more prevalent among patients with depression (46.9%) versus non-depressed comparisons (19.7%). A lower level of education, lower cognitive functioning, and more chronic diseases were independently associated with polypharmacy. Adjusted for these determinants, polypharmacy was associated with a higher level of motivational problems, anxiety, pain, and an earlier age of onset. A higher number of drugs was associated with a worse course of late-life depression (OR=1.24 [95% CI: 1.03 - 1.49], p=.022). CONCLUSION: Older patients with depression have a huge risk of polypharmacy, in particular among those with an early onset depression. As an independent risk factor for chronic depression, polypharmacy needs to be identified and managed appropriately. Findings suggest that depression moderates polypharmacy through shared risk factors, including motivational problems, anxiety, and pain. The complex interaction with somatic health burden requires physicians to prescribe medications with care

Long-term antidepressant use: a qualitative study on perspectives of patients and GPs in primary care

Background Antidepressant use is often prolonged in patients with anxiety and/or depressive disorder(s) compared with recommendations in treatment guidelines to discontinue after sustained remission. Aim To unravel the motivations of patients and GPs causing long-term antidepressant use and to gain insight into possibilities to prevent unnecessary long-term use. Design and setting Qualitative study using semi-structured, in-depth interviews with patients and GPs in the Netherlands. Method Patients with anxiety and/or depressive disorder(s) (n = 38) and GPs (n = 26) were interviewed. Innovatively, the interplay between patients and their GPs was also investigated by means of patient-GP dyads (n = 20). Results The motives and barriers of patients and GPs to continue or discontinue antidepressants were related to the availability of supportive guidance during discontinuation, the personal circumstances of the patient, and considerations of the patient or GP. Importantly, dyads indicated a large variation in policies of general practices around long-term use and continuation or discontinuation of antidepressants. Dyads further indicated that patients and GPs seemed unaware of each other's (mismatching) expectations regarding responsibility to initiate discussing continuation or discontinuation. Conclusion Although motives and barriers to antidepressant continuation or discontinuation were related to the same themes for patients and GPs, dyads indicated discrepancies between them. Discussion between patients and GPs about antidepressant use and continuation or discontinuation may help clarify mutual expectations and opinions. Agreements between a patient and their GP can be included in a patient-tailored treatment plan

Does the attention General Practitioners pay to their patients' mental health problems add to their workload? A cross sectional national survey

BACKGROUND: The extra workload induced by patients with mental health problems may sometimes cause GPs to be reluctant to become involved in mental health care. It is known that dealing with patients' mental health problems is more time consuming in specific situations such as in consultations. But it is unclear if GPs who are more often involved in patients' mental health problems, have a higher workload than other GPs. Therefore we investigated the following: Is the attention GPs pay to their patients' mental health problems related to their subjective and objective workload? METHODS: Secondary analyses were made using data from the Second Dutch National Survey of General Practice, a cross sectional study conducted in the Netherlands in 2000–2002. A nationally representative selection of 195 GPs from 104 general practices participated in this National Survey. Data from: 1) a GP questionnaire; 2) a detailed log of the GP's time use during a week and; 3) an electronic medical registration system, including all patients' contacts during a year, were used. Multiple regression analyses were conducted with the GP's workload as an outcome measure, and the GP's attention for mental health problems as a predictor. GP, patient, and practice characteristics were included in analyses as potential confounders. RESULTS: Results show that GPs with a broader perception of their role towards mental health care do not have more working hours or patient contacts than GPs with a more limited perception of their role. Neither are they more exhausted or dissatisfied with the available time. Also the number of patient contacts in which a psychological or social diagnosis is made is not related to the GP's objective or subjective workload. CONCLUSION: The GP's attention for a patient's mental health problems is not related to their workload. The GP's extra workload when dealing in a consultation with patients' mental health problems, as is demonstrated in earlier research, is not automatically translated into a higher overall workload. This study does not confirm GPs' complaints that mental health care is one of the components of their job that consumes a lot of their time and energy. Several explanations for these results are discussed

BMP signaling mediates glioma stem cell quiescence and confers treatment resistance in glioblastoma.

Despite advances in therapy, glioblastoma remains an incurable disease with a dismal prognosis. Recent studies have implicated cancer stem cells within glioblastoma (glioma stem cells, GSCs) as mediators of therapeutic resistance and tumor progression. In this study, we investigated the role of the transforming growth factor-β (TGF-β) superfamily, which has been found to play an integral role in the maintenance of stem cell homeostasis within multiple stem cell systems, as a mediator of stem-like cells in glioblastoma. We find that BMP and TGF-β signaling define divergent molecular and functional identities in glioblastoma, and mark relatively quiescent and proliferative GSCs, respectively. Treatment of GSCs with BMP inhibits cell proliferation, but does not abrogate their stem-ness, as measured by self-renewal and tumorigencity. Further, BMP pathway activation confers relative resistance to radiation and temozolomide chemotherapy. Our findings define a quiescent cancer stem cell population in glioblastoma that may be a cellular reservoir for tumor recurrence following cytotoxic therapy

GliomaPredict: a clinically useful tool for assigning glioma patients to specific molecular subtypes

<p>Abstract</p> <p>Background</p> <p>Advances in generating genome-wide gene expression data have accelerated the development of molecular-based tumor classification systems. Tools that allow the translation of such molecular classification schemas from research into clinical applications are still missing in the emerging era of personalized medicine.</p> <p>Results</p> <p>We developed GliomaPredict as a computational tool that allows the fast and reliable classification of glioma patients into one of six previously published stratified subtypes based on sets of extensively validated classifiers derived from hundreds of glioma transcriptomic profiles. Our tool utilizes a principle component analysis (PCA)-based approach to generate a visual representation of the analyses, quantifies the confidence of the underlying subtype assessment and presents results as a printable PDF file. GliomaPredict tool is implemented as a plugin application for the widely-used GenePattern framework.</p> <p>Conclusions</p> <p>GliomaPredict provides a user-friendly, clinically applicable novel platform for instantly assigning gene expression-based subtype in patients with gliomas thereby aiding in clinical trial design and therapeutic decision-making. Implemented as a user-friendly diagnostic tool, we expect that in time GliomaPredict, and tools like it, will become routinely used in translational/clinical research and in the clinical care of patients with gliomas.</p

Symptomatic and functional recovery in depression in later life

Objectives: Functional limitations give an indication of the total impact of diseases, such as depression, on individuals health and recovery. This study examines the change in several domains of functioning over 2 years in older persons depressed at baseline (non-remitted group and remitted group after 2 years) and in a non-depressed comparison group. Methods: Data were used from a cohort study (Netherlands Study of Depression in Older persons [NESDO]) consisting of depressed older persons ≥ 60 years (N = 378) and a non-depressed comparison group (N = 132) with 2 years of follow-up (attrition rate 24%). Functional limitations (outcome) were assessed with the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) questionnaire every 6 months. Total scores and domain scores were used. Depression was classified according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria at baseline and at 2-year follow-up. Severity of depression (predictor) was assessed with the Inventory of Depressive Symptomatology (IDS) at 6-month intervals. Results: Linear mixed models showed that the level of functional limitations differed between the three groups during 2 years of follow-up. The non-remitted group had the highest level of functional limitations during 2 years, followed by the remitted group. Stable low levels of functional limitations were found for the non-depressed group. Remission from depression was accompanied by improvements in functioning, however, compared to the non-depressed comparison group significant functional limitations remained. Higher severity of depression appeared as risk factor for a declining course of functioning, especially the social aspects of functioning. Methodological considerations: Participants that were more severely depressed and more functionally impaired at baseline had higher attrition rates than the participants that were included in the analytical sample. Conclusion: This study showed that depression in later life has long-term debilitating effects on functioning, enduring even after remission from depression. This implies that depression treatment in later life should aim broader than just symptomatic recovery, but also include functional recovery

Hospital Mental Health Admissions in Women after Unsuccessful Infertility Treatment and In Vitro Fertilization: An Australian Population-Based Cohort Study

Objective - To examine the association between in vitro fertilization (IVF) and later admission to hospital with a mental health diagnosis in women who remained childless after infertility treatment. Methods - This was a population-based cohort study using linked administrative hospital and registry data. The study population included all women commencing hospital treatment for infertility in Western Australia between the years 1982 and 2002 aged 20–44 years at treatment commencement who did not have a recorded birth by the end of follow-up (15 August 2010) and did not have a hospital mental health admission prior to the first infertility admission (n=6,567). Of these, 2,623 women had IVF and 3,944 did not. We used multivariate Cox regression modeling of mental health admissions and compared women undergoing IVF treatment with women having infertility treatment but not IVF. Results - Over an average of 17 years of follow-up, 411 women in the cohort were admitted to hospital with a mental health diagnosis; 93 who had IVF and 318 who did not. The unadjusted hazard ratio (HR) for a hospital mental health admission comparing women who had IVF with those receiving other infertility treatment was 0.50 (95% confidence interval [CI] 0.40–0.63). After adjustment for age, calendar year and socio-economic status the HR was 0.56 (95% CI 0.44–0.71). Conclusions - IVF treatment is associated with a reduced risk of hospital mental health admissions in women after unsuccessful infertility treatment. This may be explained by the healthy cohort effect