Lebanese Hospital-Based Rheumatoid Arthritis Registry: Characteristics of Patients and Comparison with Other Populations.

Objectives: The aim of the Lebanese hospital-based Rheumatoid Arthritis (RA) registry, initiated in 2011, is to evaluate the safety and efficacy of biologic agents among patients seeking care at the American University of Beirut Medical Center (AUBMC). We aimed to characterize the demographic and clinical profile of RA patients included in the Lebanese registry. We compared our results with those issued from Middle Eastern and non-Middle Eastern registries. Methods: 195 Patients enrolled in the RA registry from 2011 to 2018 were considered in this study. Patients enrolled in the registry were eligible to be treated with biologics, but 56 patients remained biologics naïve. Patients were reassessed every six months. Results: The highest proportion of patients were female (81%). The mean age was 55.53±15 years, and the disease duration was 11.38±7.7 years. RA was diagnosed at a mean age of 44.13±16 years. Almost one-third of RA patients were smokers (29.2%) and 15% consumed alcohol. Comorbidities included cardiac diseases (30.8%), hypertension (24.6%), hyperlipidemia (11.8%), diabetes mellitus (9.2%), and Hypothyroidism (6.2%). Three cases of cancer and seven cases of tuberculosis were reported. The mean of the Disease Activity Score (DAS28) was 3.75 ± 2.28 with no difference according to gender; the mean of the Health Assessment Questionnaire (HAQ) score showed a significant difference between females and males (1.02 ± 0.84 and 0.61 ± 0.7 respectively). Methotrexate was the most commonly used medication. There was non-significant difference in taking biologics according to gender. Conclusion: Our findings are similar to other studies in terms of gender distribution. The higher mean age at diagnosis compared to other populations could indicate a delay in seeking appropriate care. The Lebanese RA registry provides valuable data on pharmacological interventions used and an opportunity to follow up to examine the effectiveness of different therapeutics and to monitor their side effects.

The GG genotype of the serotonin 4 receptor genetic polymorphism, rs1345697, is associated with lower remission rates after antidepressant treatment: Findings from the METADAP cohort.

BACKGROUND: Pharmacological studies have yielded valuable insights into the role of the serotonin 4 receptor (HTR4) in major depressive episodes (MDE) and response to antidepressant drugs (AD). A genetic association has been shown between HTR4 and susceptibility to mood disorders. Our study aims at assessing the association between the HTR4 genetic polymorphism, rs1345697, and improvement in depressive symptoms and remission after antidepressant treatment in MDE patients. METHODS: 492 depressed patients from the METADAP cohort were treated prospectively for 6 months with ADs. The clinical outcomes according to HTR4 rs1345697 were compared after 1 (M1), 3 (M3), and 6 (M6) months of treatment. Mixed-effects logistic regression and adjusted linear models assessed the association between rs1345697 and 17-item Hamilton Depression Rating Scale (HDRS) score improvement and response/remission. RESULTS: Over the 6 months of treatment, mixed-effects regressions showed lower improvements in HDRS scores (Coefficient=1.52; Confident Interval (CI) 95% [0.37-2.67]; p = 0.009) and lower remission rates (Odds Ratio=2.0; CI95% [1.0-4.1]; p = 0.05) in GG homozygous patients as compared to allele A carriers. LIMITATIONS: The major limitations of our study are the uncertainty of the rs1345697 effect on HTR4 function, the substantial drop-out rate, and the fact that analysis is not based on randomization between polymorphism groups. CONCLUSIONS: In our study, patients who were homozygous carriers of the variant G of the HTR4 rs1345697 had lower depressive symptoms improvement and 2-fold lower remission rates after antidepressant treatment as compared to allele A carriers. Randomization study should be done to confirm these results.

Severe insomnia is associated with metabolic syndrome in women over 50 years with major depression treated in psychiatry settings: a METADAP report.

INTRODUCTION: Major depression is associated with metabolic syndrome and cardiovascular risk. We have previously shown that severe insomnia, a core symptom of major depression episode (MDE), is associated with hypertriglyceridemia, a component of metabolic syndrome, in women but not in men with major depression. Since insomnia is related to cardiovascular morbidity in the general population and major depression also, our objective was to assess the link between insomnia and metabolic syndrome, a marker syndrome of cardiovascular risk, during MDE, in women and in men. METHODS: In 624 patients with a current MDE cohort, both insomnia and metabolic syndrome were assessed in women and men. Insomnia was rated from 0 to 6 based on the HDRS corresponding items, severe insomnia being defined by a total insomnia score ≥4. RESULTS: severe insomnia was associated with metabolic syndrome in women but not in men. In multivariate logistic regressions, these results in women were independent from age, educational level, major depressive disorder duration and current smoking. These results were only significant in women aged ≥50 years, a cut-off age for menopausal status but not in women under 50 years. CONCLUSION: Women aged ≥50 years with a severe insomnia during MDE have an increased risk of metabolic syndrome. Severe insomnia may be a clinical marker of metabolic risk in this population. They should be particularly monitored for metabolic syndrome and may benefit from sleep recommendations and cardiovascular prevention.

Lower plasma vascular endothelial growth factor A in major depressive disorder not normalized after antidepressant treatment: A case control study.

OBJECTIVE: Vascular endothelial growth factor A is a growth factor with pro-angiogenic and neurotrophic properties. Anti-vascular endothelial growth factor A treatments, used to treat cancers and opthalmic diseases, are known to induce depressive symptoms. Thus, we hypothesized that vascular endothelial growth factor A plasma levels are low in patients experiencing a major depressive episode in the context of major depressive disorder, which consequently increase after antidepressant treatment. The aim of this study was to compare plasma vascular endothelial growth factor A levels in patients with major depressive episode-major depressive disorder before and after antidepressant treatment. METHODS: Vascular endothelial growth factor A fasting plasma levels of 469 major depressive episode-major depressive disorder patients were compared with healthy controls. Depressed patients were assessed for remission after 3 and 6 months of antidepressant treatment. Bivariate and multivariate analyses adjusted for sex, age, body mass index and tobacco use were performed. RESULTS: As compared to healthy controls, major depressive episode patients had lower vascular endothelial growth factor A, 66.0 (38.3) pg/mL (standard deviation) vs 83.2 (49.2) pg/mL, p < 0.0001. Plasma vascular endothelial growth factor A levels did not change after antidepressant treatment, even in remitters, and remained lower than those of healthy controls, 64.9 (39.3) pg/mL vs 83.2 (49.2) pg/mL, p < 0.0001. CONCLUSION: Depressed patients with major depressive disorder have lower plasma vascular endothelial growth factor A levels than healthy controls during their major depressive episode and after remission following antidepressant treatment. New strategies targeting enhancement of plasma vascular endothelial growth factor A could be promising for the prevention and treatment of major depressive disorder.

Early weight gain predicts later weight gain in depressed patients treated with antidepressants: Findings from the METADAP cohort.

BACKGROUND: Weight gain is a major side effect of antidepressant (AD) drugs. We assessed whether early weight gain is a predictor for long term weight gain in depressed patients treated with antidepressants. METHODS: In the six month prospective METADAP cohort, 260 non-overweight patients with a major depressive disorder (MDD), who have recently experienced a Major Depressive Episode (MDE) were assessed for early weight gain (>3%,>5%, and >7%) after one month of treatment, and for long term weight gain (>15% and >20%) after three and six months of treatment. ROC analysis was used to determine the predictive power of early weight gain. RESULTS: 12.4% (21/170) of patients became overweight after three months of treatment and 21.1% (26/123) were overweight after six months. Compared to non-early weight gainers, patients with early weight gain (>3%, >5% and >7%) were 11.3 (OR = 11.3, 95%CI: 4.6-27.6)], 9.9 (OR = 9.9, 95%CI: 3.6-26.9)] and 17.8 (OR = 17.8, 95%CI: 6.4-49.4)] times, respectively, more at risk of late weight gain (>15%). ROC analysis showed that early weight gain (>3%) after one month of treatment, was the best predictor of long term weight gain (≥15%) after three months [Area Under the Curve (AUC )= 87%] and six months of treatment (AUC = 88%) PERSPECTIVES: Given that our baseline sample consisted of strictly non-overweight patients, the 3% threshold for weight gain after one month should be used as an indicator to initiate early weight monitoring in depressed patients treated with antidepressants. High attrition rate remains a limitation in this cohort and other cohorts in psychiatric settings. DISCLOSURES: Bruno Falissard consults for and received lecture fees from for E. Lilly, BMS, Servier, Sanofi-Aventis, GlaxoSmithKline, HRA, Roche, Boeringer Ingelheim, Bayer, Almirall, Allergan, Stallergene, Genzyme, Pierre Fabre, Astra Zeneca, Novartis, Janssen, Astellas, Biotronik, Daiichi-Sankyo, Gilead, MSD, Lundbeck. Florence Gressier received lecture fees from for Servier, Lundbeck and a grant from Servier. Mircea Polosan consults for and received lecture fees from Astra-Zeneca, Bristol Myers Squibb, Lundbeck, Otsuka and Servier. Emmanuel Haffen consults for and received lecture fees from Astra-Zeneca, Bristol Myers Squibb, Pfizer, Lilly, Lundbeck, Otsuka, Sanofi-Aventis, Servier. Philippe Chanson has received unrestricted research and educational grants from Ipsen, Novartis, Novo-Nordisk, and Pfizer for the Department of Endocrinology and Reproductive Diseases, Hôpitaux Universitaires Paris-Sud and for INSERM U 693. He has served as investigator (principal or coordinator) for clinical trials funded by Novartis, Pfizer, Ipsen, Italopharmaco, Antisense, Prolor Biotech. He is member of Advisory Boards from Ipsen, Novartis, Viropharma. He gave lectures for Ipsen, Novartis, Pfizer, NovoNordisk. All the fees and honoraria were paid to his Institution. Bruno Falissard consults for and received lecture fees from NovoNordisk, MSD and Sanofi-Aventis. Laurent Bequemont has close family member working at Sanofi-Aventis, consults for Sanofi-Aventis, Pfizer, Servier and received lecture fees from Genzyme, GlaxoSmithKline, Bristol-Myers Squibb and Merck Sharp and Dohme. Khalil El Asmar, Séverine Trabado, Albane Vievard, Céline Verstuyft, Romain Colle and Emmanuelle Corruble have nothing to declare.

Glycogen synthase kinase-3ß genetic polymorphisms and insomnia in depressed patients: A prospective study.

BACKGROUND: 80-90% of patients with Major Depressive Episode (MDE) experience insomnia and up-to 50% severe insomnia. Glycogen Synthase Kinase-3ß (GSK3B) is involved both in mood regulation and circadian rhythm. Since GSK3B polymorphisms could affect protein levels or functionality, we investigated the association of GSK3B polymorphisms with insomnia in a sample of depressed patients treated with antidepressants. METHODS: In this 6-month prospective real-world treatment study in psychiatric settings (METADAP), 492 Caucasian patients requiring a new antidepressant treatment were included and genotyped for five GSK3B Single Nucleotide Polymorphisms (SNPs) (rs6808874, rs6782799, rs2319398, rs13321783, rs334558). Insomnia and MDE severity were rated using the Hamilton Depression Rating Scale (HDRS). Bi- and multivariate analyses were performed to assess the association between GSK3B SNPs and insomnia (main objective). We also assessed their association with MDE severity and HDRS response/remission after antidepressant treatment. RESULTS: At baseline severe insomnia was associated with the GSK3B rs334558 minor allele (C+) [OR=1.81, CI95%(1.17-2.80), p=0.008]. GSK3B rs334558 C+ had greater insomnia improvement after 6 months of antidepressant treatment (p=0.007, ß=0.17, t=2.736). No association was found between GSK3B SNPs and MDE baseline severity or 6-month response/remission. CONCLUSION: GSK3B rs334558 was associated with insomnia but not with MDE severity in depressed patients. Targeting GSK3B in patients with MDE and a severe insomnia could be a way to improve their symptoms with greater efficiency. And it should be further studied whether the GSK3B-insomnia association may fit into the larger picture of mood disorders.

The Catechol-O-methyltransferase Val(108/158)Met Genetic Polymorphism cannot be Recommended as a Biomarker for the Prediction of Venlafaxine Efficacy in Patients Treated in Psychiatric Settings.

The antidepressant venlafaxine is known to increase the turnover of cerebral monoamines, which are catabolized by the catechol-O-methyltransferase (COMT). The COMT (Val(108/158)Met, rs4680) genetic polymorphism affects the cerebral COMT activity. But whether this genetic polymorphism is associated with response to venlafaxine remains unclear. We assessed the impact of the COMT Val(108/158)Met, rs4680 genetic polymorphism on the efficacy of venlafaxine in depressed patients. This study was nested in the METADAP cohort, a real-world naturalistic treatment study in psychiatric settings. A total of 206 Caucasian patients with a unipolar major depressive episode (DSM-IVTR) treated with venlafaxine and evaluated with the Hamilton Depression Rating Scale (HDRS) were studied. One hundred and eighty patients were genotyped for the COMT Val(108/158)Met, rs4680 genetic polymorphism and classified into three genotype subgroups: Val/Val, Val/Met and Met/Met. The COMT genotype was the explanatory variable, and the variables to be explained were HDRS score, HDRS score improvement over time, response rate and remission rate. Venlafaxine had a trend to higher efficacy in the Val/Val patients as compared to Met/Met carriers, as shown by the HDRS score improvement after 3 months of treatment, but this result was not significant in mixed models [Val/Val: 59.78% (±22.4); Val/Met: 51.64% (±26.3); Met/Met: 39.52% (±27.6)]. The percentage of responders and remitters after 3 months of treatment was not significantly different in the three genotype groups, although coherent trends were shown. The COMT Val(108/158)Met, rs4680 genetic polymorphism cannot be recommended as a biomarker for the prediction of venlafaxine efficacy in patients treated in psychiatric settings.

Rewards and challenges of providing HIV testing and counselling services: health worker perspectives from Burkina Faso, Kenya and Uganda.

The rapid scale-up of human immunodeficiency virus (HIV) testing, counselling and treatment throughout sub-Saharan Africa has raised questions about how to protect patients' rights to consent, confidentiality, counselling and care in resource-constrained settings. The Multi-country African Testing and Counselling for HIV (MATCH) study investigated client and provider experiences with different modes of testing in sub-Saharan Africa. One component of that study was a survey of 275 HIV service providers in Burkina Faso, Kenya and Uganda that gathered quantifiable indicators and qualitative descriptions using a standardized instrument. This article presents provider perspectives on the challenges of obtaining consent, protecting confidentiality, providing counselling and helping clients manage disclosure. It also explores health workers' fear of infection within the workplace and their reports on discrimination against HIV clients within health facilities. HIV care providers in Burkina Faso, Kenya and Uganda experienced substantial rewards from their work, including satisfaction from saving lives and gaining professional skills. They also faced serious resource constraints, including staff shortages, high workloads, lack of supplies and inadequate infrastructure, and they expressed concerns about accidental exposure. Health workers described heavy emotional demands from observing clients suffer emotional, social and health consequences of being diagnosed with HIV, and also from difficult ethical dilemmas related to clients who do not disclose their HIV status to those around them, including partners. These findings suggest that providers of HIV testing and counselling need more resources and support, including better protections against HIV exposure in the workplace. The findings also suggest that health facilities could improve care by increasing attention to consent, privacy and confidentiality and that health policy makers and ethicists need to address some unresolved ethical dilemmas related to confidentiality and non-disclosure, and translate those discussions into better guidance for health workers.