104 research outputs found
Patient involvement in clinical research: Why, when, and how
The development of a patient-centered approach to medicine is gradually allowing more patients to be involved in their own medical decisions. However, this change is not happening at the same rate in clinical research, where research generally continues to be carried out on patients, but not with patients. This work describes the why, when, and how of more active patient participation in the research process. Specific measures are proposed to improve patient involvement in 1) setting priorities, 2) study leadership and design, 3) improved access to clinical trials, 4) preparation and oversight of the information provided to participants, 5) post-study evaluation of the patient experience, and 6) the dissemination and application of results. In order to achieve these aims, the relative emphases on the ethical principles underlying research need to be changed. The current model based on the principle of beneficence must be left behind, and one that upholds the ethical principles of autonomy and non maleficence should be embraced. There is a need to improve the level of information that patients and society as a whole have on research objectives and processes; the goal is to promote the gradual emergence of the expert patient
BK Lyncis: The Oldest Old Nova?... And a Bellwether for Cataclysmic-Variable Evolution
We summarize the results of a 20-year campaign to study the light curves of
BK Lyncis, a nova-like star strangely located below the 2-3 hour orbital period
gap in the family of cataclysmic variables. Two apparent "superhumps" dominate
the nightly light curves - with periods 4.6% longer, and 3.0% shorter, than
P_orb. The first appears to be associated with the star's brighter states
(V~14), while the second appears to be present throughout and becomes very
dominant in the low state (V~15.7).
Starting in the year 2005, the star's light curve became indistinguishable
from that of a dwarf nova - in particular, that of the ER UMa subclass.
Reviewing all the star's oddities, we speculate: (a) BK Lyn is the remnant of
the probable nova on 30 December 101, and (b) it has been fading ever since,
but has taken ~2000 years for the accretion rate to drop sufficiently to permit
dwarf-nova eruptions. If such behavior is common, it can explain other puzzles
of CV evolution. One: why the ER UMa class even exists (because all members can
be remnants of recent novae). Two: why ER UMa stars and short-period novalikes
are rare (because their lifetimes, which are essentially cooling times, are
short). Three: why short-period novae all decline to luminosity states far
above their true quiescence (because they're just getting started in their
postnova cooling). Four: why the orbital periods, accretion rates, and
white-dwarf temperatures of short-period CVs are somewhat too large to arise
purely from the effects of gravitational radiation (because the unexpectedly
long interval of enhanced postnova brightness boosts the mean mass-transfer
rate). These are substantial rewards in return for one investment of
hypothesis: that the second parameter in CV evolution, besides P_orb, is time
since the last classical-nova eruption.Comment: PDF, 46 pages, 4 tables, 10 figures; in preparation; more info at
http://cbastro.org
Negative cognitive schema modification as mediator of symptom improvement after electroconvulsive therapy in major depressive disorder
Background: Electroconvulsive therapy (ECT) is a potent option for treatment-resistant major depressive disorder (MDD). Cognitive models of depression posit that negative cognitions and underlying all-or-nothing negative schemas contribute to and perpetuate depressed mood. This study investigates whether ECT can modify negative schemas, potentially via memory reactivation, and whether such changes are related to MDD symptom improvement. Method: Seventy-two patients were randomized to either an emotional memory reactivation electroconvulsive therapy (EMR-ECT) or control memory reactivation electroconvulsive therapy (CMR-ECT) intervention prior to ECT-sessions in a randomized controlled trail. Emotional memories associated with patients' depression were reactivated before ECT-sessions. At baseline and after the ECT-course, negative schemas and depression severity were assessed using the Dysfunctional Attitude Scale (DAS) and Hamilton Depression Rating Scale HDRS. Mediation analyses were used to examine whether the effects of ECT on HDRS-scores were mediated by changes in DAS-scores or vice versa. Results: Post-ECT DAS-scores were significantly lower compared to baseline. Post-ECT, the mean HDRS-score of the whole sample (15.10 ± 8.65 [SD]; n = 59) was lower compared to baseline (24.83 ± 5.91 [SD]). Multiple regression analysis showed no significant influence of memory reactivation on schema improvement. Path analysis showed that depression improvement was mediated by improvement of negative cognitive schemas. Conclusion: ECT is associated with improvement of negative schemas, which appears to mediate the improvement of depressive symptoms. An emotional memory intervention aimed to modify negative schemas showed no additional effect
Genetic evolution of uveal melanoma guides the development of an inflammatory microenvironment
Experimental cancer immunology and therap
Effectiveness of Emotional Memory Reactivation vs Control Memory Reactivation Before Electroconvulsive Therapy in Adult Patients With Depressive Disorder A Randomized Clinical Trial:A Randomized Clinical Trial
Importance: Although electroconvulsive therapy (ECT) is often effective, approximately half of patients with depression undergoing ECT do not benefit sufficiently, and relapse rates are high. ECT sessions have been shown to weaken reactivated memories. The effect of emotional memory retrieval on cognitive schemas remains unknown. Objective: To assess whether emotional memory retrieval just before patients receive ECT sessions weakens underlying cognitive schemas, improves ECT effectiveness, increases ECT response, and reduces relapse rates. Design, Setting, and Participants: In this multicenter randomized clinical trial conducted from 2014 to 2018 in the departments of psychiatry in 3 hospitals in the Netherlands, 72 participants were randomized 1:1 to 2 parallel groups to receive either emotional memory reactivation (EMR-ECT) or control memory reactivation (CMR-ECT) interventions before ECT sessions. The Hamilton Depression Rating Scale (HDRS [total score range: 0-52, with 0-7 indicating no depression and ≥24 indicating severe depression]) was used to measure symptoms of depression during and after ECT, with a 6-month follow-up period. Participants were between ages 18 and 70 years with a primary diagnosis of unipolar major depressive disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) and in whom ECT was indicated. Data analysis was performed from July to November 2019. Interventions: EMR-ECT or CMR-ECT interventions prior to ECT sessions. Main Outcomes and Measures: Depression scores and relapse rates within 6 months were assessed with the HDRS and analyzed using logistic and linear multiple regression analyses. Results: A total of 66 patients (mean [SD] age, 49.3 [12.3] years; 39 [59.1%] women) were randomized to the EMR-ECT group (n = 32) or the CMR-ECT group (n = 34). Regardless of the memory intervention, 42.4% (28 of 66) of patients responded (≥50% decrease of symptom severity on the HDRS). Of patients who responded, 39.3% (11 of 28) relapsed within 6 months. Remission rates (CMR-ECT group, 29.4% [10 of 34] vs EMR-ECT group, 25.0% [8 of 32]; P = .58), mean (SD) HDRS scores after the ECT course (CMR-ECT group, 14.6 [8.6] vs EMR-ECT group, 14.9 [8.8]; P = .88), total mean (SD) number of required ECT sessions for response (CMR-ECT group, 14.9 [7.9] vs EMR-ECT group, 15.6 [7.3]; P = .39), and relapse rates (CMR-ECT group, 46.7% [7 of 15] vs EMR-ECT group, 30.8% [4 of 13]; P = .33) were not significantly altered by the intervention. Conclusions and Relevance: Study findings suggest that the EMR-ECT intervention just before patient receipt of ECT for depression did not improve effectiveness, increase speed of response, or reduce relapse rates after the ECT course compared with patients receiving CMR-ECT. Trial Registration: Trialregister.nl Identifier: NL4289
Tumour Angiogenesis in Uveal Melanoma Is Related to Genetic Evolution
Increased angiogenesis is associated with a higher metastasis- and mortality rate in uveal
melanoma (UM). Recently, it was demonstrated that genetic events, such as 8q-gain and BAP1-loss,
influence the level of immune infiltrate. We aimed to determine whether genetic events, and specific
cytokines, relate to angiogenesis in UM. Data from UM patients who underwent enucleation between
1999 and 2008 were analysed. Microvascular density (MVD) and the presence of infiltrating immune
cells were determined with immunohistochemistry (IHC) and immunofluorescence in 43 cases.
Chromosome status, BAP1 IHC and mRNA expression of angiogenesis-related genes were known
in 54 cases. Tumours with monosomy 3/BAP1-loss showed a higher MVD compared to tumours
with disomy 3/normal BAP1 expression (p = 0.008 and p = 0.004, respectively). Within BAP1-positive
lesions (n = 20), 8q-gain did not relate to MVD (p = 0.51). A high MVD was associated with an
increased expression of angiopoietin 2 (ANGPT2) (p = 0.041), Von Willebrand Factor (VWF) (p = 0.010),
a decreased expression of vascular endothelial growth factor B (VEGF-B) (p = 0.024), and increased
numbers of tumour-infiltrating macrophages (CD68+, p = 0.017; CD68+CD163+, p = 0.031) and
lymphocytes (CD4+, p = 0.027). Concluding, vascular density of UM relates to its genetic profile:
Monosomy 3 and BAP1-loss are associated with an increased MVD, while an early event (gain of 8q)
is not independently related to MVD, but may initiate a preparation phase towards development of
vessels. Interestingly, VEGF-B expression is decreased in UM with a high MVD
Evaluating the 'return on patient engagement initiatives' in medicines research and development: A literature review
Search strategy and inclusion criteria. We undertook a scoping literature review using a systematic search, including academic and grey literature with a focus on evaluation approaches or outcomes associated with patient engagement. No date limits were applied other than a cut-off of publications after July 2018. Data extraction and synthesis. Data were extracted from 91 publications, coded and thematically analysed. Main results. A total of 18 benefits and 5 costs of patient engagement were identified, mapped with 28 possible indicators for their evaluation. Several quantitative and qualitative methods were found for evaluation of benefits and costs of patient engagement.
Discussion and conclusions. Currently available indicators and methods are of some use in measuring impact but are not sufficient to understand the pathway to impact, nor whether interaction between researchers and patients leads to change. We suggest that the impacts of patient engagement can best be determined not by applying single indicators, but a coherent set of measures
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