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

Effective spinless fermions in the strong coupling Kondo model

Starting from the two-orbital Kondo-lattice model with classical t_2g spins, an effective spinless fermion model is derived for strong Hund coupling J_H with a projection technique. The model is studied by Monte Carlo simulations and analytically using a uniform hopping approximation. The results for the spinless fermion model are in remarkable agreement with those of the original Kondo-lattice model, independent of the carrier concentration, and even for moderate Hund coupling J_H. Phase separation, the phase diagram in uniform hopping approximation, as well as spectral properties including the formation of a pseudo-gap are discussed for both the Kondo-lattice and the effective spinless fermion model in one and three dimensions.Comment: Revtex4, 10 pages, 15 figures, typos correcte

A 6-year prospective clinical cohort study on the bidirectional association between frailty and depressive disorder

Introduction: Depressive disorder has been conceptualised as a condition of accelerated biological ageing. We operationalised a frailty index (FI) as marker for biological ageing aimed to explore the bidirectional, longitudinal association between frailty and either depressive symptoms or depressive disorder. Methods: A cohort study with 6-year follow-up including 377 older (≥60 years) outpatients with a DSM-IV-defined depressive disorder and 132 never-depressed controls. Site visits at baseline, 2 and 6-year follow-up were conducted and included the CIDI 2.0 to assess depressive disorder and relevant covariates. Depressive symptom severity and mortality were assessed every 6 months by mail and telephone. A 41-item FI was operationalised and validated against the 6-year morality rate by Cox regression (HRFI = 1.04 [95% CI: 1.02–1.06]). Results: Cox regression showed that a higher FI was associated with a lower chance of remission among depressed patients (HRFI = 0.98 [95% CI: 0.97–0.99]). Nonetheless, this latter effect disappeared after adjustment for baseline depressive symptom severity. Linear mixed models showed that the FI increased over time in the whole sample (B[SE] = 0.94 (0.12), p <.001) with a differential impact of depressive symptom severity and depressive disorder. Higher baseline depressive symptom severity was associated with an attenuated and depressive disorder with an accelerated increase of the FI over time. Conclusions: The sum score of depression rating scales is likely confounded by frailty. Depressive disorder, according to DSM-IV criteria, is associated with accelerated biological ageing. This argues for the development of multidisciplinary geriatric care models incorporating frailty to improve the overall outcome of late-life depression

Using theatre in education in a traditional lecture oriented medical curriculum

<p>Abstract</p> <p>Background</p> <p>Lectures supported by theatrical performance may enhance learning and be an attractive alternative to traditional lectures. This study describes our experience with using theatre in education for medical students since 2001.</p> <p>Methods</p> <p>The volunteer students, coached by experienced students, were given a two-week preparation period to write and prepare different dramatized headache scenarios during three supervised meetings. A theatrical performance was followed by a student presentation about history taking and clinical findings in diagnosing headache. Finally, a group discussion led by students dealt with issues raised in the performance. The evaluation of the theatre in education lecture "A Primary Care Approach to Headache" was based on feedback from students.</p> <p>Results</p> <p>More than 90% of 43 responding students fully agreed with the statement "Theatrical performance made it easier to understand the topic". More than 90% disagreed with the statements "Lecture halls were not appropriate for this kind of interaction" and "Students as teachers were not appropriate". Open-ended questions showed that the lesson was thought of as fun, good and useful by most students. The headache questions in the final exam showed results that were similar to average exam results for other questions.</p> <p>Conclusion</p> <p>Using theatrical performance in medical education was appreciated by most students and may facilitate learning and enhance empathy and team work communication skills.</p

Lipid-mediated Wnt protein stabilization enables serum-free culture of human organ stem cells

Wnt signalling proteins are essential for culture of human organ stem cells in organoids, but most Wnt protein formulations are poorly active in serum-free media. Here we show that purified Wnt3a protein is ineffective because it rapidly loses activity in culture media due to its hydrophobic nature, and its solubilization requires a detergent, CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate), that interferes with stem cell self-renewal. By stabilizing the Wnt3a protein using phospholipids and cholesterol as carriers, we address both problems: Wnt activity remains stable in serum-free media, while non-toxic carriers allow the use of high Wnt concentrations. Stabilized Wnt3a supports strongly increased self-renewal of organ and embryonic stem cells and the serum-free establishment of human organoids from healthy and diseased intestine and liver. Moreover, the lipophilicity of Wnt3a protein greatly facilitates its purification. Our findings remove a major obstacle impeding clinical applications of adult stem cells and offer advantages for all cell culture uses of Wnt3a protein

FOXL2 and TERT promoter mutation detection in circulating tumor DNA of adult granulosa cell tumors as biomarker for disease monitoring

OBJECTIVE: Adult granulosa cell tumors (aGCTs) represent a rare, hormonally active subtype of ovarian cancer that has a tendency to relapse late and repeatedly. Current serum hormone markers are inaccurate in reflecting tumor burden in a subset of aGCT patients, indicating the need for a novel biomarker. We investigated the presence of circulating tumor DNA (ctDNA) harboring a FOXL2 or TERT promoter mutation in serial plasma samples of aGCT patients to determine its clinical value for monitoring disease. METHODS: In a national multicenter study, plasma samples (n = 110) were prospectively collected from 21 patients with primary (n = 3) or recurrent (n = 18) aGCT harboring a FOXL2 402C > G and/or TERT (C228T or C250T) promoter mutation. Circulating cell-free DNA was extracted and assessed for ctDNA containing one of either mutations using droplet digital PCR (ddPCR). Fractional abundance of FOXL2 mutant and TERT mutant ctDNA was correlated with clinical parameters. RESULTS: FOXL2 mutant ctDNA was found in plasma of 11 out of 14 patients (78.6%) with aGCT with a confirmed FOXL2 mutation. TERT C228T or TERT C250T mutant ctDNA was detected in plasma of 4 of 10 (40%) and 1 of 2 patients, respectively. Both FOXL2 mutant ctDNA and TERT promoter mutant ctDNA levels correlated with disease progression and treatment response in the majority of patients. CONCLUSIONS: FOXL2 mutant ctDNA was present in the majority of aGCT patients and TERT promoter mutant ctDNA has been identified in a smaller subset of patients. Both FOXL2 and TERT mutant ctDNA detection may have clinical value in disease monitoring

Search for New Particles Decaying to Dijets at CDF

We have used 106 pb^-1 of data collected with the Collider Detector at Fermilab to search for new particles decaying to dijets. We exclude at the 95% confidence level models containing the following new particles: axigluons and flavor universal colorons with mass between 200 and 980 GeV/c, excited quarks with mass between 80 and 570 GeV/c^2 and between 580 and 760 GeV/c^2, color octet technirhos with mass between 260 and 480 GeV/c^2, W' bosons with mass between 300 and 420 GeV/c^2, and E_6 diquarks with mass between 290 and 420 GeV/c^2.Comment: 18 pages, 4 figures, 1 table. Submitted to Physical Review D Rapid Communications. Postscript file of paper is also available at http://www-cdf.fnal.gov/physics/pub97/cdf3276_dijet_search_prd_rc.p