Assessment of an enhanced program for depression management in primary care: a cluster randomized controlled trial. The INDI project (Interventions for Depression Improvement)

<p>Abstract</p> <p>Background</p> <p>Most depressed patients are attended at primary care. However, there are significant shortcomings in the diagnosis, management and outcomes of these patients. The aim of this study is to determine whether the implementation of a structured programme for managing depression will provide better health outcomes than usual management.</p> <p>Methods/Design</p> <p><it>Design</it>: A cluster-randomized controlled trial involving two groups, one of which is the control group consisting of patients who are treated for depression in the usual way and the other is the intervention group consisting of patients on a structured programme for treating depression.</p> <p><it>Setting</it>: 20 primary care centres in the province of Tarragona (Spain)</p> <p><it>Sample</it>: 400 patients over 18 years of age who have experienced an episode of major depression (DSM-IV) and who need to initiate antidepressant treatment</p> <p><it>Intervention</it>: A multi-component programme with clinical, educational and organisational procedures that includes training for the health care provider and evidence-based clinical guidelines. It also includes primary care nurses working as care-managers who provide educational and emotional support for the patients and who are responsible for active and systematic clinical monitoring. The programme aims to improve the primary care/specialized level interface.</p> <p><it>Measurements</it>: The patients will be monitored by telephone interviews. The interviewer will not know which group the patient belongs to (blind trial). These interviews will be given at 0, 3, 6 and 12 months.</p> <p><it>Main variables</it>: Severity of the depressive symptoms, response rate and remission rate.</p> <p><it>Analysis</it>: Outcomes will be analyzed on an intent-to-treat basis and the unit of analysis will be the individual patient. This analysis will take into account the effect of study design on potential lack of independence between observations within the same cluster.</p> <p>Discussion</p> <p>The effectiveness of caring for depression in primary care can be improved by various strategies. The most effective models involve organisational changes and a greater role of nurses. However, these models are almost exclusively from the USA, and this randomized clinical trial will determine if this approach could be effective to improve the outcomes of depression in primary care in the Spanish health care system.</p> <p>Trial registration</p> <p>ISRCTN16384353</p

Ultrabright Föster Resonance Energy Transfer Nanovesicles:The Role of Dye Diffusion

The development of contrast agents based on fluorescent nanoparticles with high brightness and stability is a key factor to improve the resolution and signal-to-noise ratio of current fluorescence imaging techniques. However, the design of bright fluorescent nanoparticles remains challenging due to fluorescence self-quenching at high concentrations. Developing bright nanoparticles showing FRET emission adds several advantages to the system, including an amplified Stokes shift, the possibility of ratiometric measurements, and of verifying the nanoparticle stability. Herein, we have developed Förster resonance energy transfer (FRET)-based nanovesicles at different dye loadings and investigated them through complementary experimental techniques, including conventional fluorescence spectroscopy and super-resolution microscopy supported by molecular dynamics calculations. We show that the optical properties can be modulated by dye loading at the nanoscopic level due to the dye's molecular diffusion in fluid-like membranes. This work shows the first proof of a FRET pair dye's dynamism in liquid-like membranes, resulting in optimized nanoprobes that are 120-fold brighter than QDot 605 and exhibit >80% FRET efficiency with vesicle-to-vesicle variations that are mostly below 10%.J.M.-F. gratefully thanks the financial support received by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 712949 (TECNIOspring PLUS) and from the Agency for Business Competitiveness of the Government of Catalonia. We acknowledge the European Commission (EC) FP7-PEOPLE-2013-Initial Training Networks (ITN) “NANO2FUN” project no. 607721 for being the spark that initiates this work and EC project MSCA-RISE-2020 "MICRO4NANO" project no.101007804. This work was also financially supported by Generalitat de Catalunya (grant no. 2017-SGR-918), the Ministry of Economy, Industry, and Competitiveness (Spain), through the “MOTHER” project (MAT2016-80826-R), the Ministry of Science and Innovation of Spain through the grant PID2019-105622RB-I00 (Mol4Bio). ICMAB-CSIC also acknowledges support from the MINECO through the Severo Ochoa Programme FUNFUTURE (SEV-2015-0496 and CEX2019-000917-S). K.D.B. acknowledges the National Science Foundation (CBET-1517273 and CHE-1726345). C.S. and A.P. benefited from the equipment and framework of the COMP-HUB Initiative, funded by the “Departments of Excellence” program of the Italian Ministry for Education, University and Research (MIUR, 2018-2022). We thank the CESGA Supercomputing Center for technical support and the use of computational resources. The contribution of S.I.-T. has been done under the Materials Science PhD program in the Barcelona Autonomous University (UAB). Characterizations of nanovesicles were made at the ICTS “NANBIOSIS”, more specifically by the U6 unit of CIBER-BBN. The authors would like also to thank the collaboration of Hamamatsu Photonics for the quantum yield determinations using the Quantaurus-QY Plus UV–NIR absolute PL quantum yield spectrometer.With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).Peer reviewe

Unraveling the genetics of transformed splenic marginal zone lymphoma

Altres ajuts: Fundació La Marató de TV3 (201904-30)The genetic mechanisms associated with splenic marginal zone lymphoma (SMZL) transformation are not well defined. We studied 41 patients with SMZL that eventually underwent large B-cell lymphoma transformation. Tumor material was obtained either only at diagnosis (9 patients), at diagnosis and transformation (18 patients), and only at transformation (14 patients). Samples were categorized in 2 groups: (1) at diagnosis (SMZL, n = 27 samples), and (2) at transformation (SMZL-T, n = 32 samples). Using copy number arrays and a next-generation sequencing custom panel, we identified that the main genomic alterations in SMZL-T involved TNFAIP3, KMT2D, TP53, ARID1A, KLF2, 1q gains, and losses of 9p21.3 (CDKN2A/B) and 7q31-q32. Compared with SMZL, SMZL-T had higher genomic complexity, and higher incidence of TNFAIP3 and TP53 alterations, 9p21.3 (CDKN2A/B) losses, and 6p gains. SMZL and SMZL-T clones arose by divergent evolution from a common altered precursor cell that acquired different genetic alterations in virtually all evaluable cases (92%, 12 of 13 cases). Using whole-genome sequencing of diagnostic and transformation samples in 1 patient, we observed that the SMZL-T sample carried more genomic aberrations than the diagnostic sample, identified a translocation t(14;19)(q32;q13) present in both samples, and detected a focal B2M deletion due to chromothripsis acquired at transformation. Survival analysis showed that KLF2 mutations, complex karyotype, and International Prognostic Index score at transformation were predictive of a shorter survival from transformation (P =.001; P =.042; and P =.007; respectively). In summary, SMZL-T are characterized by higher genomic complexity than SMZL, and characteristic genomic alterations that could represent key players in the transformation event

Unraveling the genetics of transformed splenic marginal zone lymphoma

The genetic mechanisms associated with splenic marginal zone lymphoma (SMZL) transformation are not well defined. We studied 41 patients with SMZL that eventually underwent large B-cell lymphoma transformation. Tumor material was obtained either only at diagnosis (9 patients), at diagnosis and transformation (18 patients), and only at transformation (14 patients). Samples were categorized in 2 groups: (1) at diagnosis (SMZL, n = 27 samples), and (2) at transformation (SMZL-T, n = 32 samples). Using copy number arrays and a next-generation sequencing custom panel, we identified that the main genomic alterations in SMZL-T involved TNFAIP3, KMT2D, TP53, ARID1A, KLF2, 1q gains, and losses of 9p21.3 (CDKN2A/B) and 7q31-q32. Compared with SMZL, SMZL-T had higher genomic complexity, and higher incidence of TNFAIP3 and TP53 alterations, 9p21.3 (CDKN2A/B) losses, and 6p gains. SMZL and SMZL-T clones arose by divergent evolution from a common altered precursor cell that acquired different genetic alterations in virtually all evaluable cases (92%, 12 of 13 cases). Using whole-genome sequencing of diagnostic and transformation samples in 1 patient, we observed that the SMZL-T sample carried more genomic aberrations than the diagnostic sample, identified a translocation t(14;19)(q32;q13) present in both samples, and detected a focal B2M deletion due to chromothripsis acquired at transformation. Survival analysis showed that KLF2 mutations, complex karyotype, and International Prognostic Index score at transformation were predictive of a shorter survival from transformation (P = .001; P = .042; and P = .007; respectively). In summary, SMZL-T are characterized by higher genomic complexity than SMZL, and characteristic genomic alterations that could represent key players in the transformation event

Flowchart: randomisation of centres, and sampling and monitoring of patients

<p><b>Copyright information:</b></p><p>Taken from "Assessment of an enhanced program for depression management in primary care: a cluster randomized controlled trial. The INDI project (Interventions for Depression Improvement)"</p><p>http://www.biomedcentral.com/1471-2458/7/253</p><p>BMC Public Health 2007;7():253-253.</p><p>Published online 20 Sep 2007</p><p>PMCID:PMC2094706.</p><p></p