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.
Aims:
Patients with a first episode of psychosis (FEP) often display different metabolic disturbances even independently of drug therapy. However, antipsychotic (AP) treatment, especially with ...second-generation APs, is strongly linked to weight gain, which increases patients’ risk of developing obesity and other metabolic diseases. There is an important genetic risk component that can contribute to the appearance of these disturbances. The aim of the present study was to evaluate the effect of polymorphisms in selected candidate genes on obesity and other anthropometric and metabolic traits in 320 AP-treated FEP patients over the course of a 2-year follow-up.
Methods:
These patients were recruited in the multicentre PEPs study (Phenotype−genotype and environmental interaction; Application of a predictive model in first psychotic episodes). A total of 127 validated single nucleotide polymorphisms (SNPs) in 18 candidate genes were included in the genetic analysis.
Results:
After Bonferroni correction, SNPs in ADRA2A, FTO, CNR1, DRD2, DRD3, LEPR and BDNF were associated with obesity, abdominal circumference, triglycerides, HDL cholesterol, and/or percentage of glycated haemoglobin.
Conclusions:
Although our results should be interpreted as exploratory, they support previous evidence of the impact of these candidate genes on obesity and metabolic status. Further research is required to gain a better knowledge of the genetic variants that can be considered relevant metabolic risk factors. The ability to identify FEP patients at higher risk for these metabolic disturbances would enable clinicians to better select and control their AP treatment.
Attachment style, which has been theorized to be rooted in childhood bonding experiences, influences adult cognitive, emotional and interpersonal functioning. Despite its relationship with early ...experiences, research indicates that the continuity of attachment style across childhood and adulthood is only partial, being a malleable tendency that is shaped throughout development, with an increasing influence of genetics, as it occurs in other cognitive and behavioral phenotypes. Genetic research indicates that up to 45% of the variability in anxious and 39% in avoidant adult attachment style could be explained by genetic causes, but the precise mechanisms remain unclear. A narrative review is conducted analyzing the existing literature regarding the implication of candidate genes related to oxytocin, dopaminergic pathways, serotonergic pathways and brain-derived neurotrophic factor in adult attachment, with both vulnerability and differential susceptibility approaches, yielding mixed results. We highlight the lack of genome-wide studies and the scarcity of epigenetic investigation. Based on the existing data, we conclude that the genetics of adult attachment is an area that requires further research to clarify its etiological role and that it should be preferably approached as an interaction between nature and nurture.
Abstract We report a case of an 11-year-old columbian immigrant with mild non-specific cephalalgia. He had a previous history of frontal fracture and skin infestation caused by Dermatobia hominis ...larvae. MRI performed revealed multiple subependymal and intraventricular lesions with concentric blooming artifacts and moderate hydrocephalus. Based on his previous history, intracerebral myiasis diagnosis was suggested. His mother denied any kind of diagnostic surgery or treatment. To the best of our knowledge, this is the first MRI report of a possible intracerebral myiasis, an exceedingly rare entity.
Process evaluation studies are recommended to improve our understanding of underlying mechanisms related to clinicians, patients, context and intervention delivery that may impact on trial or program ...results and on their potential transferability to practice. This paper aims to document the translation of a type-2 diabetes (T2D) prevention program into the routine context of several primary care centers, assessing process indicators related to clinician adoption, patient recruitment, exposure to the intervention components and baseline characteristics.
An observational descriptive process evaluation study was conducted of the 2.5-year implementation of the Prevention of Diabetes in Euskadi cluster randomized trial in 14 primary care centers of the Basque Health Service (Osakidetza). The clinical intervention consisted of three components: (1) risk screening, (2) an educational intervention promoting healthy lifestyles, and (3) remote support (follow-up). A passive dissemination strategy of providing training and materials was used to translate the intervention into practice. All non-diabetic patients aged 45 to 70 years who were identified as being at high risk of developing T2D were eligible for study inclusion. The RE-AIM framework guided the process evaluation.
Overall, 31.4 % of family physicians and 57.6 % of nurses participated in the study, while 4170 out of 67,293 (6.2 %) targeted patients who attended the centers during the implementation period were reached through the screening. Around half of the screened patients were identified as being at high risk of developing T2D (FINDRISC score ≥14). The rate of refusal to participate and the proportion of women were higher in the intervention group. Finally, 634 and 454 non-diabetic 45- to 70-year-old patients who were at high risk of T2D were included in the control and intervention group centers (intervention reach = 48 %). Significant variability in most process indicators was observed at center level.
The passive dissemination strategy has produced modest process indicators related to the adoption, reach and implementation of the intervention program, and reduced the possibility of its standardized application in heterogeneous contexts. The resulting different procedures and strategies used by the centers were associated with process outcomes. Context-specific variability and possible confounding will require rigorous procedures for analysis of the intervention effects.
The trial was registered in ClinicalTrials.gov (identifier: NCT01365013 ). Registered on June 2011.
Animal-derived, protein-containing surfactants seem to be superior to protein-free surfactants. Lucinactant, a synthetic surfactant containing a surfactant protein-B peptide analog, has been shown to ...be effective in animal models and phase II clinical trials. To date, lucinactant has not been compared with an animal-derived surfactant in a premature animal model.
The objective was to compare the acute and sustained effects of lucinactant among premature lambs with respiratory distress syndrome (RDS) with the effects of a natural porcine surfactant (poractant-alpha).
After 5 minutes of mechanical ventilation twin premature lambs were assigned randomly to the lucinactant group (30 mg/mL, 5.8 mL/kg) or the poractant-alpha group (80 mg/mL, 2.2 mL/kg). Heart rate, systemic arterial pressure, arterial pH, blood gas values, and lung mechanics were recorded for 12 hours.
Baseline fetal pH values were similar for the 2 groups (pH 7.27). After 5 minutes of mechanical ventilation, severe RDS developed (pH: <7.08; Paco2: >80 mm Hg; Pao2: <40 mm Hg; dynamic compliance: <0.08 mL/cm H2O per kg). After surfactant instillation, similar improvements in gas exchange and lung mechanics were observed for the lucinactant and poractant-alpha groups at 1 hour (pH: 7.3 +/- 0.1 vs 7.4 +/- 0.1; Paco2: 8 +/- 18 mm Hg vs 40 +/- 8 mm Hg; Pao2: 167 +/- 52 mm Hg vs 259 +/- 51 mm Hg; dynamic compliance: 0.3 +/- 0.1 mL/cm H2O per kg vs 0.3 +/- 0.1 mL/cm H2O per kg). The improvements in lung function were sustained, with no differences between groups. Cardiovascular profiles remained stable in both groups.
Among preterm lambs with severe RDS, lucinactant produced improvements in gas exchange and lung mechanics similar to those observed with a porcine-derived surfactant.
A modified vaccinia Ankara-based HIV-1 vaccine clade B (MVA-B) has been tested for safety and immunogenicity in low-risk human immunodeficiency virus (HIV)-uninfected individuals and as a therapeutic ...vaccine in HIV-1-infected individuals on combined antiretroviral therapy (cART). As a therapeutic vaccine, MVA-B was safe and broadly immunogenic; however, patients still showed a viral rebound upon treatment interruption. Monocytes are an important part of the viral reservoir and several studies suggest that they are partly responsible for the chronic inflammation observed in cART-treated HIV-infected people. The CD300 family of receptors has an important role in several diseases, including viral infections. Monocytes express CD300a, c, e, and f molecules and lipopolysaccharide (LPS) and other stimuli regulate their expression. However, the expression and function of CD300 receptors on monocytes in HIV infection is still unknown. In this work, we investigated for the first time the expression of CD300 molecules and the cytokine production in response to LPS on monocytes from HIV-1-infected patients before and after vaccination with MVA-B. Our results showed that CD300 receptors expression on monocytes from HIV-1-infected patients correlates with markers of HIV infection progression and immune inflammation. Specifically, we observed a positive correlation between the expression of CD300e and CD300f receptors on monocytes with the number of CD4+ T cells of HIV-1-infected patients before vaccination. We also saw a positive correlation between the expression of the inhibitory receptor CD300f and the expression of CD163 on monocytes from HIV-1-infected individuals before and after vaccination. In addition, monocytes exhibited a higher cytokine production in response to LPS after vaccination, almost at the same levels of monocytes from healthy donors. Furthermore, we also described a correlation in the expression of CD300e and CD300f receptors with TNF-α production in response to LPS, only in monocytes of HIV-1-infected patients before vaccination. Altogether, our results describe the impact of HIV-1 and of the MVA-B vaccine in cytokine production and monocytes phenotype.
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