[Show abstract][Hide abstract] ABSTRACT: Adherence to evidence-based cardiovascular (CV) medications after an acute myocardial infarction (AMI) is low after the first 6 months. The use of fixed-dose combinations (FDC) has been shown to improve treatment adherence and risk factor control. However, no previous randomized trial has analyzed the impact of an FDC strategy on adherence in post-MI patients.
Journal of the American College of Cardiology 08/2014; · 15.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: : Fluoxetine (FLX) has been one of the most widely studied selective serotonin reuptake inhibitors in adolescents. Despite its efficacy, however, 30% to 40% of patients do not respond to treatment.
The aim of this study was to evaluate whether clinical improvement or adverse events are related to the corrected dose of FLX at 8 and 12 weeks after starting treatment in a sample of adolescents diagnosed with major depressive disorder, obsessive-compulsive disorder, or generalized anxiety disorder.
Seventy-four subjects aged between 10 and 17 years participated in the study. Clinical improvement was measured with the Clinical Global Impression-Improvement Scale, whereas the UKU (Udvalg for Klinske Undersogelser) scale was administered to assess adverse effects of treatment.
Fluoxetine per kilograms of body weight was related to serum concentration of FLX, NORFLX (norfluoxetine), FLX + NORFLX, and FLX/NORFLX. No relationship was found between dose-corrected FLX levels and therapeutic or adverse effects. No differences in serum concentrations were found between responders and nonresponders to treatment. Sex differences were observed in relation to dose and FLX serum concentration. The analysis by diagnosis revealed differences in FLX dose between obsessive-compulsive disorder patients and both generalized anxiety disorder and major depressive disorder patients.
Fluoxetine response seems to be influenced by factors such as sex, diagnosis, or certain genes that might be involved in the drug's pharmacokinetics and pharmacodynamics. Clinical and pharmacogenetic studies are needed to elucidate further the differences between treatment responders and nonresponders.
Journal of clinical psychopharmacology 04/2014; · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aim: To elucidate the relationship between CYP2D6 genotype and risperidone pharmacokinetics and extrapyramidal symptoms we propose the APSEP pharmacogenetic clinical trial. Materials & methods: Twenty-five healthy subjects were included in this randomized, placebo-controlled, single dose (risperidone 2.5 mg) crossover and double-blind clinical trial. Subjects were selected according to their CYP2D6 genotype and classified as: poor metabolizers (n = 8), extensive metabolizers (n = 10) and ultrarapid metabolizers (n = 7). Results & conclusion: Our study demonstrates that CYP2D6 predicted 65% of the risperidone metabolism variability. Moreover, its ability to predict actigraphy records is similar to the predictive power of pharmacokinetic parameters (24%). Our results also highlight the need for the development of pharmacogenetic predictors that take into account the complexity of pharmacokinetic and pharmacodynamic relationships.
[Show abstract][Hide abstract] ABSTRACT: Background: CD4+ count increase has been reported to be different with lopinavir/r (LPV/r) and efavirenz (EFV)-containing regimens. The different effect of these two regimens on other immune function parameters and the relationship with the gain of CD4+ count have not been assessed in a randomized clinical trial. Methods: Fifty antiretroviral (cART) naïve-HIV-infected individuals were randomized to receive LPV/r or EFV both with tenofovir/emtricitabine during 48 weeks. A substudy of immunological function restoration was performed in 22 patients (LPV/r n=10 and EFV n=12). Activation, thymic function, apoptosis, senescence, exhaustion, Treg cells, IL-7-receptor/IL-7 system, thymic volume and lymphoid tissue fibrosis were evaluated at baseline and at week 48. Results: Both groups experienced CD4+ count increase that was higher in the EFV group (∆CD4+ 88 vs 315 cells/L LPV/r vs EFV, respectively, p<0.001). Despite this difference in CD4+ gain, the change in other immune function parameters was similar in both treatment groups. Most of parameters evaluated tended to normalize after 48 weeks of cART. A significant decrease in levels of activation, senescence, exhaustion and apoptosis on CD4+ and CD8+ T cells (p<0.001 for all), and a significant increase in markers of thymic function, IL-7-receptor and in the levels of central memory CD4+ T cells and naïve subsets of CD8+ T cells (p<0.001 for all) with respect to baseline values was observed without difference between groups. Conclusions: These data support that the differences in CD4+ gain with different cART regimen are not immunologically meaningful and might explain the similar clinical efficacy of these regimens. Key Words: HIV, antiretroviral therapy, immune reconstitution.
AIDS research and human retroviruses 12/2013; · 2.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aim: This study aimed to elucidate the relationship between CYP2D6 genotype and haloperidol pharmacokinetics and induced extrapyramidal symptoms (EPSs). Materials & methods: Twenty five healthy subjects were included in this randomized, placebo-controlled, single-dose (5 mg) crossover and double-blind clinical trial, selected according to their CYP2D6 genotype and classified as poor metabolizers (n = 8), extensive metabolizers (n = 10) and ultrarapid metabolizers (n = 7). Results & conclusion: We confirm that CYP2D6 genotype partially determines haloperidol metabolism and the rate of EPSs measured as wakefulness activity by actigraphy. The best predictor of wakefulness activity was the model including haloperidol area under the plasma concentration-time curve, sex and tranquilization, which explained 48.3% of the total variance. However, other markers need to be identified in order to explain the observed variability of haloperidol response and to develop pharmacogenetic predictors of haloperidol-induced EPSs.
[Show abstract][Hide abstract] ABSTRACT: A clinical trial comparing the rate of discontinuation and tolerability of two post-exposure prophylaxis (PEP) regimens was performed.
A total of 255 individuals attending the emergency rooms of six hospitals for exposure to HIV and criteria to receive PEP were randomized to receive zidovudine/lamivudine plus either lopinavir/ritonavir (n=131) or atazanavir (n=124; day 0). The primary end point was the rate of PEP discontinuation before day 28 of follow-up. Secondary end points were incidence of side effects, follow-up at days 90 and 180 and rate of seroconversions.
A total of 55 patients (29 in lopinavir/ritonavir and 26 in atazanavir arms) did not attend the first scheduled appointment (day 1) and were excluded from the analysis. The rate of discontinuation before day 28 owing to any cause was similar between groups (37/102 [36%] in lopinavir/ritonavir and 35/98 [36%] in atazanavir arms, P=0.82). Adverse events were the reason for discontinuation or switching of PEP in 33 individuals (16/102 [16%] in the lopinavir/ritonavir arm and 17/98 [17%] in the atazanavir arm, P=0.84). Adverse events were reported in 92/200 (46%) of individuals on PEP who attend at least the day 1 appointment (50/102 [49%] in the lopinavir/ritonavir arm and 42/98 [43%] in the atazanavir arm, P=0.38). There were no seroconversions.
The rate of discontinuation of PEP before day 28 was similar with zidovudine/lamivudine plus either lopinavir/ritonavir or atazanavir. The rate of discontinuation of PEP because of adverse events was low in both arms. Almost 50% of the patients of both arms suffered side effects. New strategies are needed to improve the tolerance.
[Show abstract][Hide abstract] ABSTRACT: In spite of advances in prevention and treatment, the burden of cardiovascular diseases is increasing. A fixed-dose combination (FDC) pill, or "polypill," composed of evidence-based drugs has been proposed as a means of improving cardiovascular prevention by reducing cost and increasing patient adherence to treatment. The aim of the FOCUS project, funded by the 7th Framework Programme of the European Commission, is to characterize the factors that underlie inadequate secondary prevention and to test a new FDC. To achieve these goals, a 9-member consortium has been constituted, including institutions from Argentina, France, Italy, Spain, and Switzerland. FOCUS Phase-1 will examine factors potentially related to lack of adequate secondary prevention in 4,000 post-myocardial infarction (MI) patients and analyze the relationship between these factors and patient treatment adherence. Primary end points will be (1) the percentage of patients receiving aspirin, angiotensin-converting enzyme inhibitors, and statins and (2) adherence to treatment measured by the Morisky-Green test. FOCUS Phase-2 is a randomized trial that will compare adherence to treatment in 1,340 post-myocardial infarction patients either receiving an FDC comprising aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and simvastatin (40 mg) or receiving the same 3 drugs separately.
American heart journal 11/2011; 162(5):811-817.e1. · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the safety and immunogenicity of a modified vaccinia virus Ankara vector expressing HIV-1 antigens from clade B (MVA-B), a phase-I, doubled-blind placebo-controlled trial was performed.
30 HIV-uninfected volunteers at low risk of HIV-1 infection were randomly allocated to receive 3 intramuscular injections (1×10(8)pfu/dose) of MVA-B (n=24) or placebo (n=6) at weeks 0, 4 and 16. All volunteers were followed 48 weeks. Primary end-points were adverse events and immunogenicity.
A total of 169 adverse events were reported, 164 of grade 1-2, and 5 of grade 3 (none related to vaccination). Overall 75% of the volunteers showed positive ELISPOT responses at any time point. The magnitude (median) of the total responses induced was 288SFC/10(6)PBMC at week 18. Antibody responses against Env were observed in 95% and 72% of vaccinees at week 18 and 48, respectively. HIV-1 neutralizing antibodies were detected in 33% of volunteers.
MVA-B was safe, well tolerated and elicited strong and durable T-cell and antibody responses in 75% and 95% of volunteers, respectively. These data support further exploration of MVA-B as an HIV-1 vaccine candidate. Clinical Trials.gov identifier: NCT00679497.
[Show abstract][Hide abstract] ABSTRACT: Data comparing abacavir/lamivudine versus tenofovir/emtricitabine in antiretroviral-naive patients are controversial. We compared 48-week efficacy and safety of these combinations as substitutes of nucleosides in patients with virological suppression.
We randomly assigned 333 HIV-1-infected patients on lamivudine-containing triple regimens with <200 copies per milliliter for at least 6 months to switch their nucleosides to either abacavir/lamivudine (n = 167) or tenofovir/emtricitabine (n = 166). The primary outcome was treatment failure ["switching = failure" intention to treat (ITT) analysis, noninferiority margin 12.5%]. Secondary outcomes were time to treatment failure, virological failure, adverse events, and changes in CD4 count, fasting plasma lipids, lipodystrophy, body fat, bone mineral density, and renal function.
Treatment failure occurred in 32 patients (19%) on abacavir/lamivudine and 22 patients (13%) on tenofovir/emtricitabine [difference 5.9%; (95% confidence interval -2.1% to 14.0%), P = 0.06]. Four patients in the abacavir/lamivudine group versus none in the tenofovir/emtricitabine group developed virological failure [difference 2.4; (95% confidence interval 0.05 to 6.0), P = 0.04]. Twenty-three patients (14%) assigned to abacavir/lamivudine and 10 (6%) to tenofovir/lamivudine experienced grade 3 or 4 adverse effects (P = 0.03). CD4 counts and plasma lipids showed higher increments in the abacavir/lamivudine group than in the tenofovir/emtricitabine group.
In HIV-1-infected patients with virological suppression, abacavir/lamivudine did not meet the noninferiority outcome for treatment efficacy compared with tenofovir/emtricitabine.
[Show abstract][Hide abstract] ABSTRACT: The effects of conjugated linoleic acid (CLA) on body weight and body composition in man are controversial. The aim of this study was to investigate the effects of milk supplementation with CLA on body composition and on the biochemical parameters of the metabolic syndrome. This was a randomised, double-blind, placebo-controlled trial. Subjects were randomised to a daily intake of 500 ml milk supplemented with 3 g CLA (using a mixture of the bioactive isomers cis-9, trans-11 and trans-10, cis-12, marketed as Tonalin, Naturlinea; Central Lechera Asturiana) or placebo for 12 weeks. Sixty healthy men and women (aged 35-65 years) with signs of the metabolic syndrome participated (BMI 25-35 kg/m2). Dual-energy X-ray absorptiometry was used to measure body composition (week 0 baseline and week 12). Total fat mass in the CLA-milk subgroup with a BMI < or = 30 kg/m2 decreased significantly while no changes were detected in the placebo group (approximately 2 %, P = 0.01). Trunk fat mass showed a trend towards reduction (approximately 3 %, P = 0.05). CLA supplementation had no significant effect on the parameters of the metabolic syndrome, nor was it associated with changes in haematological parameters or renal function. The supplementation of milk with 3 g CLA over 12 weeks results in a significant reduction of fat mass in overweight but not in obese subjects. CLA supplementation was not associated with any adverse effects or biological changes.
British Journal Of Nutrition 11/2007; 98(4):860-7. · 3.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Stavudine (d4T)-containing regimens are associated with a potential for lipoatrophy and dyslipidaemia. We assessed the safety and efficacy of reducing the dose of stavudine compared with switching to tenofovir or maintaining the standard dose of d4T.
Clinically stable HIV-infected patients receiving antiretroviral therapy containing stavudine 40 mg twice daily with a plasma HIV RNA < 200 copies/ml for at least 6 months were randomized to maintain stavudine 40 mg twice daily (d4T40 arm), to reduce to 30 mg twice daily (d4T30 arm), or to switch from d4T to tenofovir (TDF arm).
Fifty-eight (93% male) patients were included: 22 in the d4T40 arm, 19 in the d4T30 arm and 17 in TDF arm. At baseline, median time on d4T was 6 years (interquartile range [IQR] 2.6-7.1), median age 43 years (IQR 36-51) and median CD4+ T-cell count was 587/mm3 (IQR 329-892). At week 24, median limb fat changes (g) were as follows: d4T40 = -182 (95% CI: -469- -5); d4T30 = 527 (95% CI: -343-694); and TDF = 402 (95% CI: 130-835; d4T40 versus TDF, P = 0.0003). Significant differences between median values of laboratory parameters were detected: triglycerides (mg/dl): d4T40 = 19; d4T30 = -23 and TDF = -79 (d4T40 versus TDF, P = 0.03); and total cholesterol (mg/dl): d4t40 = 22, d4T30 = -4, and TDF = -28 (d4T40 versus TDF, P = 0.04). No significant difference was observed in mitochondrial function assessed in peripheral blood mononuclear cells.
Although both strategies were associated with a trend toward a decrease in plasma lipids and an increase in body fat, the only significant changes were observed among those who switched to tenofovir.
[Show abstract][Hide abstract] ABSTRACT: To evaluate health-related quality of life (HRQoL) changes in patients treated with indinavir three-times daily after switching to a twice-daily indinavir/ritonavir regimen or continuing with the same regimen.
Patients on HAART including indinavir three-times-daily with undetectable viral load were randomly assigned to continue with this therapy or to change to a twice-daily indinavir/ritonavir (800/100 mg) regimen. The Medical Outcomes Study HIV Health Survey (MOS-HIV) questionnaire was used as the HRQoL measure.
A total of 118 patients participated in the study, of which 59 (50%) were randomly assigned to continue with the three-times-daily regimen. Patients had a mean age of 39 years and 80% of them were male. At baseline, subjects included in the three-times-daily group presented a significantly greater number of symptoms than subjects in the twice-daily group, but no statistically significant differences were observed in MOS-HIV scores between the groups. In the intention-to-treat (ITT) analysis, a reduction in HRQoL scores was observed in both groups, which was greater in the twice-daily group. In the per protocol analysis, reduction of HRQoL was minimal.
A HRQoL deterioration, greater in the twice-daily group, was observed in this study in the ITT analysis, while HRQoL remained stable in both groups in patients who continued with and tolerated the allocated regimen.