OBJECTIVE: Open-label trials with the selective serotonin reuptake inhibitor citalopram suggest that this agent is effective and safe for the treatment of depressive symptoms in children and ...adolescents. The current study investigated the efficacy and safety of citalopram compared with placebo in the treatment of pediatric patients with major depression. METHOD: An 8-week, randomized, double-blind, placebo-controlled study compared the safety and efficacy of citalopram with placebo in the treatment of children (ages 7-11) and adolescents (ages 12-17) with major depressive disorder. Diagnosis was established with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. Patients (N=174) were treated initially with placebo or 20 mg day of citalopram, with an option to increase the dose to 40 mg day at week 4 if clinically indicated. The primary outcome measure was score on the Children's Depression Rating Scale-Revised; the response criterion was defined as a score of ≤28. RESULTS: The overall mean citalopram dose was approximately 24 mg day. Mean Children's Depression Rating Scale-Revised scores decreased significantly more from baseline in the citalopram treatment group than in the placebo treatment group, beginning at week 1 and continuing at every observation point to the end of the study (effect size=2.9). The difference in response rate at week 8 between placebo (24%) and citalopram (36%) also was statistically significant. Citalopram treatment was well tolerated. Rates of discontinuation due to adverse events were comparable in the placebo and citalopram groups (5.9% versus 5.6%, respectively). Rhinitis, nausea, and abdominal pain were the only adverse events to occur with a frequency exceeding 10% in either treatment group. CONCLUSIONS: In this population of children and adolescents, treatment with citalopram reduced depressive symptoms to a significantly greater extent than placebo treatment and was well tolerated.
ObjectivesDuring the last years, genome-wide association studies (GWASs) have identified a number of common genetic risk factors for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). ...However, the genetic overlap between these two immune-mediated diseases has not been thoroughly examined so far. The aim of the present study was to identify additional risk loci shared between RA and SLE.MethodsWe performed a large-scale meta-analysis of GWAS data from RA (3911 cases and 4083 controls) and SLE (2237 cases and 6315 controls). The top-associated polymorphisms in the discovery phase were selected for replication in additional datasets comprising 13 641 RA cases and 31 921 controls and 1957 patients with SLE and 4588 controls.ResultsThe rs9603612 genetic variant, located nearby the COG6 gene, an established susceptibility locus for RA, reached genome-wide significance in the combined analysis including both discovery and replication sets (p value=2.95E−13). In silico expression quantitative trait locus analysis revealed that the associated polymorphism acts as a regulatory variant influencing COG6 expression. Moreover, protein–protein interaction and gene ontology enrichment analyses suggested the existence of overlap with specific biological processes, specially the type I interferon signalling pathway. Finally, genetic correlation and polygenic risk score analyses showed cross-phenotype associations between RA and SLE.ConclusionsIn conclusion, we have identified a new risk locus shared between RA and SLE through a meta-analysis including GWAS datasets of both diseases. This study represents the first comprehensive large-scale analysis on the genetic overlap between these two complex disorders.
A strong scientific rationale exists for conducting clinical pharmacology studies in target populations because local factors such as genetics, environment, comorbidities, and diet can affect ...variability in drug responses. However, clinical pharmacology studies are not widely conducted in sub‐Saharan Africa, in part due to limitations in technical expertise and infrastructure. Since 2012, a novel public‐private partnership model involving research institutions and a pharmaceutical company has been applied to developing increased capability for clinical pharmacology research in multiple African countries.
Abstract
Background
Despite remarkable achievements in antiretroviral therapy (ART), losses to follow-up (LTFU) might prevent the long-term success of HIV treatment and might delay the achievement of ...the 90–90-90 objectives. This scoping review is aimed at the description and analysis of the strategies used in high-income countries to reengage LTFU in HIV care, their implementation and impact.
Methods
A scoping review was done following Arksey & O′Malley’s methodological framework and recommendations from Joanna Briggs Institute. Peer reviewed articles were searched for in Pubmed, Scopus and Web of Science; and grey literature was searched for in Google and other sources of information. Documents were charted according to the information presented on LTFU, the reengagement procedures used in HIV units in high-income countries, published during the last 15 years. In addition, bibliographies of chosen articles were reviewed for additional articles.
Results
Twenty-eight documents were finally included, over 80% of them published in the United States later than 2015. Database searches, phone calls and/or mail contacts were the most common strategies used to locate and track LTFU, while motivational interviews and strengths-based techniques were used most often during reengagement visits. Outcomes like tracing activities efficacy, rates of reengagement and viral load reduction were reported as outcome measures.
Conclusions
This review shows a recent and growing trend in developing and implementing patient reengagement strategies in HIV care. However, most of these strategies have been implemented in the United States and little information is available for other high-income countries. The procedures used to trace and contact LTFU are similar across reviewed studies, but their impact and sustainability are widely different depending on the country studied.
Introduction
Migrants are overrepresented in the European HIV epidemic. We aimed to understand the barriers and facilitators to HIV testing and current treatment and healthcare needs of migrants ...living with HIV in Europe.
Methods
A cross‐sectional study was conducted in 57 HIV clinics in nine countries (Belgium, Germany, Greece, Italy, The Netherlands, Portugal, Spain, Switzerland and United Kingdom), July 2013 to July 2015. HIV‐positive patients were eligible for inclusion if they were as follows: 18 years or older; foreign‐born residents and diagnosed within five years of recruitment. Questionnaires were completed electronically in one of 15 languages and linked to clinical records. Primary outcomes were access to primary care and previous negative HIV test. Data were analysed using random effects logistic regression. Outcomes of interest are presented for women, heterosexual men and gay/bisexual men.
Results
A total of 2093 respondents (658 women, 446 heterosexual men and 989 gay/bisexual men) were included. The prevalence of a previous negative HIV test was 46.7%, 43.4% and 82.0% for women, heterosexual and gay/bisexual men respectively. In multivariable analysis previous testing was positively associated with: receipt of post‐migration antenatal care among women, permanent residency among heterosexual men and identifying as gay rather than bisexual among gay/bisexual men. Access to primary care was found to be high (>83%) in all groups and was strongly associated with country of residence. Late diagnosis was common for women and heterosexual men (60.8% and 67.1%, respectively) despite utilization of health services prior to diagnosis. Across all groups almost three‐quarters of people on antiretrovirals had an HIV viral load <50 copies/mL.
Conclusions
Migrants access healthcare in Europe and while many migrants had previously tested for HIV, that they went on to test positive at a later date suggests that opportunities for HIV prevention are being missed. Expansion of testing beyond sexual health and antenatal settings is still required and testing opportunities should be linked with combination prevention measures such as access to PrEP and treatment as prevention.
Background: Depression often coexists with a number of disease states, and patients with a diagnosis of depression often receive multiple medications. Thus, it is desirable to avoid coadministration ...of agents that have a potential for drug interactions in these patients. Although escitalopram and its metabolites are weak to negligible inhibitors of the cytochrome P450 (CYP) 3A4 isozyme and are therefore unlikely to affect plasma concentrations of ritonavir (a CYP3A4 substrate and prototype CYP3A4 inhibitor), ritonavir may potentially affect plasma concentrations of escitalopram, as CYP3A4 is partially responsible for conversion of escitalopram to its major metabolite, S-demethylcitalopram (S-DCT).
Objectives: The aim of this study was to investigate the potential for pharmacokinetic interaction between escitalopram and ritonavir after concomitant administration of a single dose of each in healthy young subjects.
Methods: In this single-center, randomized, open-label, 3-way crossover study, subjects received each of the following: a single dose of escitalopram 20 mg, a single dose of ritonavir 600 mg, and single doses of both escitalopram 20 mg and ritonavir 600 mg. Blood was collected and plasma was analyzed for the pharmacokinetic parameters (maximum plasma concentration Cmax, time to Cmax Tmax, area under the plasma concentration-time curve, plasma elimination half-life, oral clearance, and apparent volume of distribution) of escitalopram, S-DCT, and ritonavir.
Results: Of 21 subjects (11 men, 10 women; mean SD age, 28.4 4.4 years) who were enrolled, 18 completed the study. After concomitant administration of escitalopram and ritonavir, no statistically significant differences were noted in the pharmacokinetics of escitalopram, with the exception of apparent volume of distribution, which was reduced by ∼10% (P < 0.001). The pharmacokinetics of S-DCT were unaffected by coadministration of ritonavir, with the exception of Tmax, which was increased in the presence of ritonavir. The pharmacokinetic parameters of ritonavir were also unaffected by coadministration of escitalopram.
Conclusion: In general, no pharmacokinetic interaction was observed between escitalopram and ritonavir in the present study.
The evolution of research activity during the last thirty years on regenerative periodontal surgery is studied.
A small number of authors are highly productive with more than 10 publications on the ...subject each. 79,6% of authors have only produced one article on the subject. The co-authorship average is of 2,68 authors per paper, with a collaboration between 2 and 6 authors. Main journals on the field of regenerative periodontal surgery are Journal of Periodontology and Journal of Clinical Periodontology, which are ranked 14th and 1st in their category according to the Journal Citations Reports. The most used language is English, followed by Japanese and Italian, Spanish occupying the eighth position.
A significant increase on scientific literature is observed, similar to the one Dentistry has had. A reduced number of authors account for most production. In the same token, there is a scarce professionalization of researchers in this field, where most of the authors are occasional. On the other hand, there are two very specialized journals on this topic. Key words:Bibliometrics, scientometrics periodontal regeneration, surgical periodontal treatment, scientific literature, scopus, scientific output.
We use the new growth theory framework and panel cointegration techniques to analyse the effect of international agricultural technological spillovers on total factor productivity growth for a sample ...of 47 countries during the period 1970–1992. The analysis shows that total factor productivity is strongly influenced by domestic as well as foreign public research and development (R&D) spending in the agricultural sector. Geographical factors matter, in that countries located in temperate zones benefit from technological spillovers more than countries located in tropical zones. We find that the rate of return to agricultural R&D spending is higher in tropical countries. This could justify new support and an even greater investment in agricultural R&D for these countries.
Background:
Citalopram tablets fulfill most dosing needs in the treatment of depression, but some patients may have difficulty swallowing tablets and thus may be less likely to comply with their ...medication regimen. A liquid formulation of citalopram could be beneficial for such patients.
Objective:
This study was undertaken to compare the pharmacokinetic profiles of oral solution and tablet formulations of citalopram in healthy volunteers.
Methods:
In this open-label, single-dose, randomized, crossover, bioequivalence study, healthy volunteers alternately received one 60-mg dose of citalopram as an oral solution (10 mg/5 mL) and one 60-mg dose as a tablet. Doses were separated by a 14-day interval.
Results:
Of 24 subjects enrolled (mean age 27 years), 24 (16 men and 8 women) received the citalopram oral solution and 23 (15 men and 8 women) received the tablet; 1 subject discontinued before receiving the tablet. Citalopram was rapidly absorbed, with peak plasma concentrations occurring at ∼4 hours with both formulations. The rate and extent of absorption were similar between the 2 formulations, and no statistically significant differences were observed in half-life or oral clearance between formulations. Similarly, the pharmacokinetic profile for demethylcitalopram (the major metabolite of citalopram) did not differ between the 2 formulations. Both formulations were well tolerated, with no serious adverse events reported.
Conclusion:
The oral solution and tablet formulations of citalopram 60 mg were determined to be bioequivalent in this population.
Backgroundand objectives There is only one biologic agent approved for use in SLE, but some are used off-label in various settings. To obtain information systematically regarding this, members of the ...SLICC group initiated the International Registry for Biologics in SLE (IRBIS). The objective of this study was to analyse the use of biologics in SLE, and assess results achieved with the most commonly used off-label biologic, rituximab (RTX). Materials and methods IRBIS investigators were asked to provide retrospective data on all patients treated with a biologic for SLE at their center. Standardised case report forms were used to collect demographic, disease-specific and treatment data at the time of biologic initiation and at yearly follow-up. Data from the first 23 reporting centers are presented. Results Three hundred and fifty-nine patients were treated off-label with RTX, and additional groups of patients were exposed to belimumab (n=44), epratuzumab (n=21), abatacept (n=4), etanercept (n=3) and adalimumab (n=1). For the RTX treated group, age (mean±SD) was 41.3±13.3 and 91% were female. The majority (76%) were Caucasian, and smaller proportions were Southeast Asian, Asian/Indian, African-American, Latino, Afro-Caribbean or other (each <10%). Disease duration when RTX was initiated was 9.2±7.8 years. SLEDAI at start was 11.3±7.6, SLICC-damage index 1.4±1.5 and glucocorticoid dosage 17.0±15.2 mg. Most patients (78%) had been treated with one or two different immunosuppressives (ISs) prior to RTX, and the remaining with three to five ISs. Two dosing regimens were used for RTX: 375 mg/m2x4 (52%) and 1000 mgx2 (48%). The major organ manifestations leading to RTX treatment were lupus nephritis (LN, 48%), haematological (21%), musculoskeletal, skin disease, CNS and other (each <10%). At 1-year follow-up both SLEDAI and GC dose had decreased (4.2±3.5 (n=106) and 7.9±7.0mg (n=89), respectively, paired samples, p<0.0001 for both comparisons). Exclusion of patients started on additional ISs (n=24) did not change SLEDAI or GC dose significantly. SLEDAI at baseline was higher in LN than in non-LN patients but similar at follow-up. Overall, the 1000 mgx2 was more often used but both dosing regimens appeared equally effective in LN. Conclusions RTX was the off-label biologic most commonly used in this multi-center international lupus cohort and was used for LN as well as for other SLE manifestations. At one-year-follow-up both lupus activity and concomitant glucocorticoid dosage had decreased even when no other IS treatments had been introduced. The two RTX dosing regimes appeared equally effective for LN treatment, but firm conclusions cannot be made from these observational data.
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