Translation and validation of the Cardiac Depression Scale to Arabic

Background The Cardiac Depression Scale (CDS) has been designed to measure depressive symptoms in patients with heart disease. There is no Arabic version of the CDS. We translated and validated the CDS in an Arabic sample of patients with heart disease. Methods Forward and back translation of the CDS was followed by assessment of cultural relevance and content validity. The Arabic version of the CDS (A-CDS) and the Arabic version of the Hospital Anxiety and Depression Scale (A-HADS) were then administered to 260 Arab in-patients with heart disease from 18 Arabic countries. Construct validity was assessed using exploratory factor analysis with polychoric correlations. Internal consistency was assessed using ordinal reliability alpha and item-to-factor polychoric correlations. Concurrent validity was assessed using Pearson's correlation coefficient between the A-CDS and the depression subscale of the A-HADS (A-HADS-D). Results Cultural relevance and content validity of the A-CDS were satisfactory. Exploratory factor analysis revealed three robust factors, without cross-loadings, that formed a single dimension. Internal consistency was high (ordinal reliability alpha for the total scale and the three factors were .94, .91, .86, and .87, respectively; item-to-factor correlations ranged from .77 to .91). Concurrent validity was high (r?=?.72). The A-CDS demonstrated a closer to normal distribution of scores than the A-HADS-D. Limitations Sensitivity and specificity of the A-CDS were not objectively assessed. Conclusions The A-CDS appears to be a valid and reliable instrument to measure depressive symptoms in a representative sample of Arab in-patients with heart disease

Modelling imperfect adherence to HIV induction therapy

Abstract Background Induction-maintenance therapy is a treatment regime where patients are prescribed an intense course of treatment for a short period of time (the induction phase), followed by a simplified long-term regimen (maintenance). Since induction therapy has a significantly higher chance of pill fatigue than maintenance therapy, patients might take drug holidays during this period. Without guidance, patients who choose to stop therapy will each be making individual decisions, with no scientific basis. Methods We use mathematical modelling to investigate the effect of imperfect adherence during the inductive phase. We address the following research questions: 1. Can we theoretically determine the maximal length of a possible drug holiday and the minimal number of doses that must subsequently be taken while still avoiding resistance? 2. How many drug holidays can be taken during the induction phase? Results For a 180 day therapeutic program, a patient can take several drug holidays, but then has to follow each drug holiday with a strict, but fairly straightforward, drug-taking regimen. Since the results are dependent upon the drug regimen, we calculated the length and number of drug holidays for all fifteen protease-sparing triple-drug cocktails that have been approved by the US Food and Drug Administration. Conclusions Induction therapy with partial adherence is tolerable, but the outcome depends on the drug cocktail. Our theoretical predictions are in line with recent results from pilot studies of short-cycle treatment interruption strategies and may be useful in guiding the design of future clinical trials

Histone Deacetylase Inhibitor Romidepsin Induces HIV Expression in CD4 T Cells from Patients on Suppressive Antiretroviral Therapy at Concentrations Achieved by Clinical Dosing

Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation of HIV expression in latently infected cells is being explored as one of the strategies to deplete the latent HIV reservoir. In this study, we characterized the ability of romidepsin (RMD), a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC50 = 4.5 nM) compared with vorinostat (VOR; EC50 = 3,950 nM) and other histone deacetylase (HDAC) inhibitors in clinical development including panobinostat (PNB; EC50 = 10 nM). The HIV induction potencies of RMD, VOR, and PNB paralleled their inhibitory activities against multiple human HDAC isoenzymes. In both resting and memory CD4 T cells isolated from HIV-infected patients on suppressive combination antiretroviral therapy (cART), a 4-hour exposure to 40 nM RMD induced a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour treatment with 1 μM VOR resulted in 2- to 3-fold increases. RMD-induced intracellular HIV RNA expression persisted for 48 hours and correlated with sustained inhibition of cell-associated HDAC activity. By comparison, the induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours. RMD also increased levels of extracellular HIV RNA and virions from both memory and resting CD4 T-cell cultures. The activation of HIV expression was observed at RMD concentrations below the drug plasma levels achieved by doses used in patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression ex vivo at concentrations that can be achieved clinically, indicating that the drug may reactivate latent HIV in patients on suppressive cART

The macrophage in HIV-1 infection: From activation to deactivation?

Macrophages play a crucial role in innate and adaptative immunity in response to microorganisms and are an important cellular target during HIV-1 infection. Recently, the heterogeneity of the macrophage population has been highlighted. Classically activated or type 1 macrophages (M1) induced in particular by IFN-γ display a pro-inflammatory profile. The alternatively activated or type 2 macrophages (M2) induced by Th-2 cytokines, such as IL-4 and IL-13 express anti-inflammatory and tissue repair properties. Finally IL-10 has been described as the prototypic cytokine involved in the deactivation of macrophages (dM). Since the capacity of macrophages to support productive HIV-1 infection is known to be modulated by cytokines, this review shows how modulation of macrophage activation by cytokines impacts the capacity to support productive HIV-1 infection. Based on the activation status of macrophages we propose a model starting with M1 classically activated macrophages with accelerated formation of viral reservoirs in a context of Th1 and proinflammatory cytokines. Then IL-4/IL-13 alternatively activated M2 macrophages will enter into the game that will stop the expansion of the HIV-1 reservoir. Finally IL-10 deactivation of macrophages will lead to immune failure observed at the very late stages of the HIV-1 disease

Association Between Depressive Symptoms and Exercise Capacity in Patients With Heart Disease: A META-ANALYSIS

Purpose: Depression and reduced exercise capacity are risk factors for poor prognosis in patients with heart disease, but the relationship between the 2 is unclear. We assessed the relationship between depressive symptoms and exercise capacity in patients with heart disease. Methods: PubMed, Cochrane Library, Google Scholar, and ProQuest databases were browsed for English-language studies published from January 2000 to September 2013. Studies including adult patients with coronary artery disease, heart failure, congenital heart disease, and implantable cardioverter defibrillator, reporting correlation between a depression scale and exercise capacity (VO2peak, peak watts, estimated metabolic equivalents, and incremental shuttle walk test distance), as well as studies from which such a correlation could be calculated and provided by the authors, were included. Correlation coefficients (CCs) were converted to Fischer z values, and the analysis was performed using a random-effects model. Then, summary effects and 95% CIs were converted back to CCs. Results: Fifty-nine studies (25 733 participants) were included. Depressive symptoms were inversely correlated to exercise capacity (CC = -0.15; 95% CI, -0.17 to -0.12). Heterogeneity was significant (I = 64%; P < .001). There was no evidence of publication bias (Fail-safe N = 4681; Egger test: P = .06; Kendall test: P = .29). Conclusions: Patients with heart disease and elevated depressive symptoms may tend to have reduced exercise capacity, and vice versa. This finding has clinical and prognostic implications. It also encourages research on the effects of improving depression on exercise capacity, and vice versa. The effects of potential moderators need to be explored

Analysis of output modifier adaptation for real-time optimization

In the context of real-time optimization, modifier-adaptation schemes update the model-based optimization problem by adding first-order correction terms to the cost and constraint functions of the optimization problem. This guarantees meeting the plant first-order optimality conditions upon convergence, despite the presence of parametric and structural plant-model mismatch. An alternative modifier-adaptation strategy has been proposed, wherein the first-order corrections are applied to the output functions rather than to the cost and constraint functions. This paper analyzes this alternative adaptation scheme in detail and provides arguments for its use in cases where the cost and constraints are nonlinear functions of the inputs and outputs. The approach is illustrated in simulation on the Williams-Otto continuous stirred-tank reactor. (C) 2018 Elsevier Ltd. All rights reserved

Treatment of intermediate- and high-grade non-Hodgkin&apos;s lymphoma using CEOP versus CNOP - A Hellenic Co-operative Oncology Group Study

Introduction: During the last few years epirubicin (E) and mitoxantrone (M) (Novantrone) have been used in the treatment of non-Hodgkin’s lymphoma (NHL), because of their favorable principal profile. In particular, M has less severe non-hematological toxicity. Patients and methods: A randomized multicenter phase III study was conducted in order to compare the efficacy and toxicity of CEOP (arm A) consisted of cyclophosphamide 1000 mg m(-2), vincristine 2 mg, E 70 mg m(-2) on day 1 and prednisone 60 mg on days 1-7. The CNOP regimen (arm B) General Hospital, Athens, Greece was identical to CEOP except for replacement of E by M at a dose of 12 Mg m(-2). Randomization was stratified according to stages I-IV. From September 1993 to March 1999, 249 patients registered for the trial. Patient characteristics were equally distributed in the two arms, except for age and International Prognostic Index (IPI) groups. Results: There were no significant differences between the two groups in the rates of complete (CR) and partial response (PR). The overall response rate was 78% in arm A (57% CR, 2 1 % PR) and 82% in arm B (60% CR, 22% PR). With a median follow-up time of 47.3 months, the median survival was not reached in arm A, while it was 39.5 months in arm B (P=0.09). Three-year survival rates were 62.5% for CEOP and 51.5% for CNOP. There was no significant difference regarding the time to progression between the two groups (29.7 vs. 18.5 months); furthermore the median duration of CRs was 71.6 and 49 months for CEOP and CNOP, respectively (P = 0.07). The therapeutic efficacies of both regimens were equivalent among the four IPI groups. More alopecia was observed in arm A. WHO grade &gt;2 neutropenia was more frequent in arm B. Supportive treatment with G-CSF was given to 22 and 24 patients respectively. Conclusion: There were no significant differences in terms of CEOP, CNOP overall response rates, overall survival and time to progression between CEOP and CNOP in the treatment of intermediate- and high-grade NHL.Patients with low or low intermediate IPI risk treated with either Hospital, Athens 106 76, Greece CEOP or CNOP showed significantly better survival, response rates and time to progressionthan those with high intermediate or high IPI risk. Therefore, new improved therapeutic approaches should be developed for the treatment of high IPI risk patients