Objectives: This randomized, double-blind, non-inferiority trial evaluated the efficacy and safety of pharmacokinetically enhanced amoxicillin/clavulanate 2000/125 mg twice daily versus ...amoxicillin/clavulanate 875/125 mg three times daily, both given orally for 7 or 10 days, in the treatment of adults with community-acquired pneumonia in Spain, a country with a high prevalence of penicillin-resistant Streptococcus pneumoniae. Patients and methods: Following 2:1 randomization, 566 patients (intent-to-treat population) received either amoxicillin/clavulanate 2000/125 mg (n = 374) or amoxicillin/clavulanate 875/125 mg (n = 192). Results: Among the patients who did not deviate from the protocol (clinical per-protocol population), clinical success at day 21–28 post-therapy (test of cure; primary efficacy endpoint) was 92.4% (266/288) for amoxicillin/clavulanate 2000/125 mg and 91.2% (135/148) for amoxicillin/clavulanate 875/125 mg (treatment difference, 1.1; 95% confidence interval, −4.4, 6.6). Bacteriological success at test of cure in the bacteriology per-protocol population was 90.8% (79/87) with amoxicillin/clavulanate 2000/125 mg and 86.0% (43/50) with amoxicillin/clavulanate 875/125 mg (treatment difference 4.8; 95% confidence interval, −6.6, 16.2). At test of cure, amoxicillin/clavulanate 2000/125 mg was clinically and bacteriologically effective against 7/7 penicillin-resistant Streptococcus pneumoniae (MIC ≥2 mg/L) isolates (including three amoxicillin non-susceptible strains) and amoxicillin/clavulanate 875/125 mg against 5/5 isolates (including one amoxicillin non-susceptible strain). Conclusions: Both treatment regimens were well tolerated. Amoxicillin/clavulanate 2000/125 mg was at least as effective clinically and as safe as amoxicillin/clavulanate 875/125 mg in the treatment of community-acquired pneumonia in adults in a country with a high prevalence of penicillin-resistant S. pneumoniae and has a more convenient twice daily posology.
There is evidence that HIV-positive injecting drug users benefit less than other risk groups from highly active antiretroviral therapy that has been available since 1996. In this multicentre European ...study the impact of the availability of highly active antiretroviral therapy on the progression rates to AIDS and death among injecting drug users with a documented date of HIV seroconversion is studied. After highly active antiretroviral therapy became available the risk of AIDS and death for injecting drug users decreased by 28% and 36%, which is less than has been reported for other risk groups.
An HIV-Positive Man with Tattoo Induration López-Medrano, Francisco; Costa, José Ramón; Rodríguez-Peralto, José Luis ...
Clinical infectious diseases,
07/2007, Letnik:
45, Številka:
2
Journal Article
Nucleotide-binding cystathionine β-synthase (CBS) domains function as regulatory motifs in several proteins distributed through all kingdoms of life. This function has been proposed based on their ...affinity for adenosyl-derivatives, although the exact binding mechanisms remain largely unknown. The question of how CBS domains exactly work is relevant because in humans, several genetic diseases have been associated with mutations in those motifs. In this work, we describe the adenosyl-ligand (AMP, ATP, NADP and SAM) properties of the wild-type CBS domain protein MJ0729 from Methanocaldococcus jannaschii by using a combination of spectroscopic techniques (fluorescence, FTIR and FRET). The fluorescence results show that binding to AMP and ATP occurs with an apparent dissociation constant of ∼10 µM, and interestingly enough, binding induces protein conformational changes, as shown by FTIR. On the other hand, fluorescence spectra (FRET and steady-state) did not change upon addition of NADP and SAM to MJ0729, suggesting that tryptophan and/or tyrosine residues were not involved in the recognition of those ligands; however, there were changes in the secondary structure of the protein upon addition of NADP and SAM, as shown by FTIR (thus, indicating binding to the nucleotide). Taken together, these results suggest that: (i) the adenosyl ligands bind to MJ0729 in different ways, and (ii) there are changes in the protein secondary structure upon binding of the nucleotides.
Dermoscopic features of common inflammatory dermatoses are not well studied and previous reports on this topic are limited to the search of vascular features (capillaroscopy).
Dermoscopic features of ...psoriasis and lichen planus (LP) are investigated to determine both vascular and nonvascular features of these two dermatoses.
Dermoscopic images of 25 patients with LP and 20 patients with plaque psoriasis (PP) were evaluated. Findings were statistically analyzed including the reproducibility of scoring (Cohen's kappa statistics).
Our observations clearly showed that the evaluation of both vascular and nonvascular findings improved the surface microscopy of these diseases. A vascular feature (homogeneous red globules) was the most significant dermoscopic finding in the PP dermoscopic pattern (20/20, 100%; p < 0.001). A nonvascular feature (whitish striae) was the most significant dermoscopic feature in the LP pattern (23/25, 92%; p < 0.001). Dermoscopic features of LP also included gray-blue dots, comedo, milium-like cysts, and vascular structures (red lines). The intraobserver and interobserver reproducibility of scoring was very high (k value, 0.9).
Our study shows for the first time that the efficacy of surface microscopy of common inflammatory dermatoses may be improved by investigating both vascular and nonvascular findings and its practicability in daily practice by using the dermoscope. Although dermoscopy does not provide clear additional help in the clinical differentiation between typical PP and LP, it could be helpful in patients with darker skin and for teaching settings.
The SAFEHEART study was designed to analyze the situation of familial heterozygous hypercholesterolemia (FHH) and improve knowledge of this disease in Spain. Our objective was to determine the ...incidence rate of cardiovascular events, the estimated risk of developing an event and its modification, the use of lipid-lowering treatment, and the achievement of low-density lipoprotein cholesterol targets in patients with FHH.
SAFEHEART is a prospective, open, multicenter, nationwide cohort study, with long-term protocol-based follow-up in a population of individuals with molecularly-characterized FHH. We analyzed patients older than 18 years with complete follow-up.
We included 2648 patients with FHH. The median follow-up was 6.6 (4.8-9.7) years. The overall incidence rate of cardiovascular events was 1.3 events/100 patient-years. After the follow-up, the 10-year estimated risk of developing a cardiovascular event was reduced from 1.6% to 1.3% (P <.001). In the last follow-up, 20.6% and 22.2% of the patients in primary and secondary prevention achieved low-density lipoprotein cholesterol values <100mg/dL and <70mg/dL, respectively.
This study was performed in the largest population of patients with FHH in Spain. We identified the incidence rate of cardiovascular events, the estimated risk of developing a cardiovascular event and its modification, the achievement of low-density lipoprotein cholesterol targets, and the therapeutic management in this population. Although the cardiovascular risk of FHH is high, appropriate treatment reduces the likelihood of an event.
Clinical trial registration: http://www.clinicaltrials.gov. Identifier: NCT02693548.
El estudio SAFEHEART se diseñó para analizar la situación y mejorar el conocimiento de la hipercolesterolemia familiar heterocigota (HFH) en España. Nuestro objetivo es determinar la tasa de incidencia de eventos cardiovasculares, el riesgo estimado de sufrir un evento y su modificación, el empleo de tratamiento hipolipemiante y la consecución de objetivos de colesterol unido a lipoproteínas de baja densidad en pacientes con HFH.
El SAFEHEART es un estudio prospectivo de cohorte, abierto, multicéntrico, de escala nacional, con seguimiento protocolizado a largo plazo en una población de HFH caracterizada molecularmente. Se analizó a los pacientes mayores de 18 años con seguimiento completo.
El análisis en este estudio se hizo con 2.648 pacientes con HFH. La mediana de seguimiento fue de 6,6 (4,8-9,7) años. La tasa de incidencia general de eventos cardiovasculares fue de 1,3 eventos/100 pacientes-año. El riesgo estimado de sufrir un evento cardiovascular a 10 años se redujo en el seguimiento, y pasó del 1,6 al 1,3% (p <0,001). En el último seguimiento, el 20,6 y el 22,2% de los pacientes en prevención primaria y secundaria consiguieron un colesterol unido a lipoproteínas de baja densidad <100 y <70mg/dl respectivamente.
En este estudio se muestra la tasa de incidencia de eventos cardiovasculares, el riesgo estimado de sufrir un evento cardiovascular en la mayor población de pacientes con HF en España, así como su modificación, la consecución de objetivos en colesterol unido a lipoproteínas de baja densidad y su tratamiento. Aunque el riesgo cardiovascular de la HFH es elevado, un adecuado tratamiento reduce la probabilidad de sufrir un evento.
Estudio registrado en ClinicalTrials.gov (Identificador: NCT02693548).
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