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Serrano-Villar S.,Institute Investigacion Sanitaria del Hospital Clinico San Carlos IdISSC | Estrada V.,Institute Investigacion Sanitaria del Hospital Clinico San Carlos IdISSC | Gomez-Garre D.,Institute Investigacion Sanitaria del Hospital Clinico San Carlos IdISSC | Avila M.,Complutense University of Madrid | And 5 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2012

Introduction: HIV-infected patients present increased incidence of cardiovascular disease (CVD). Although incipient kidney function impairment has been associated with CVD in the general population, this association has not been properly addressed in HIV-infected patients. We assessed the relationship between incipient renal impairment (IRI) and subclinical atherosclerosis in HIV-infected patients. Methods: Estimated glomerular filtration rate (eGFR), carotid intima-media thickness (cIMT), and cardiovascular biomarkers were measured in 145 HIV-infected patients. IRI was defined as a composite variable: eGFR< 90 mL/min, rate of eGFR decrease > 3% annually over a period of 3 years, and albumin/creatinine urine ratio above the median (≥ 5 mg/g). Individuals with a cIMT ≥ 75th percentile or plaque were classified as having subclinical atherosclerosis. Results: Ninety-five patients (64.1%) met the criteria for IRI. As for HIV-related factors, patients with IRI more frequently had lipodystrophy (41.3% vs. 21.6%; P = 0.017), a lower CD4 lymphocyte nadir [210 (125-343) vs. 302 (178-408) cells/mL; P = 0.046], and longer exposure to nucleoside reverse transcriptase inhibitors [187 (84-259) vs. 104 (34-170) months; P = 0.001], to nonnucleoside reverse transcriptase inhibitors [32 (7-77) vs. 20 0-40) months; P = 0.043], and to protease inhibitors [42 (0-115] vs. 2.5 (0-59) months; P = 0.007]. Patients with IRI more frequently had subclinical atherosclerosis (40.7% vs. 13.7%; odds ratio: 4.3; 95% confidence interval: 1.8 to 10.6; P = 0.001), even after adjustment for cardiovascular and HIV-related parameters (odds ratio: 3.8; 95% confidence interval: 1.3 to 11; P = 0.012). Conclusions: The presence of IRI is an independent predictor of increased cIMT in HIV-infected patients and may help to identify patients with subclinical atherosclerosis and, therefore, increased risk of CVD. Copyright © 2012 Lippincott Williams & Wilkins.


Arranz A.,ETH Zurich | Dong D.,CAS Institute of Automation | Zhu S.,Xidian University | Rudin M.,ETH Zurich | And 6 more authors.
Optics Express | Year: 2013

A new technique termed Helical Optical Projection Tomography (hOPT) has been developed with the aim to overcome some of the limitations of current 3D optical imaging techniques. hOPT is based on Optical Projection Tomography (OPT) with the major difference that there is a translation of the sample in the vertical direction during the image acquisition process, requiring a new approach to image reconstruction. Contrary to OPT, hOPT makes possible to obtain 3D-optical images of intact long samples without imposing limits on the sample length. This has been tested using hOPT to image long murine tissue samples such as spinal cords and large intestines. Moreover, 3D-reconstructed images of the colon of DSS-treated mice, a model for Inflammatory Bowel Disease, allowed the identification of the structural alterations. Finally, the geometry of the hOPT device facilitates the addition of a Selective Plane Illumination Microscopy (SPIM) arm, providing the possibility of delivering high resolution images of selected areas together with complete volumetric information. ©2013 Optical Society of America.


Serrano-Villar S.,Hospital Clinico San Carlos | Estrada V.,Hospital Clinico San Carlos | Estrada V.,Institute Investigacion Sanitaria del Hospital Clinico San Carlos IdISSC | Gomez-Garre D.,Institute Investigacion Sanitaria del Hospital Clinico San Carlos IdISSC | And 8 more authors.
European Journal of Preventive Cardiology | Year: 2014

Aims: While the detection of subclinical atherosclerosis may provide an opportunity for the prevention of cardiovascular disease (CVD), which currently is a leading cause of death in HIV-infected subjects, its diagnosis is a clinical challenge. We aimed to compare the agreement and diagnostic performance of Framingham, SCORE and D:A:D equations for the recognition of subclinical atherosclerosis in HIV patients and to adjust the D:A:D equation using HIV and CVD variables. Methods and results: Atherosclerosis was evaluated in 203 HIV-infected individuals by measuring the carotid intimamedia thickness (IMT). The CVD risk was calculated using the Framingham, SCORE and D:A:D risk equations. Framingham, SCORE and D:A:D equations showed a low agreement with the IMT (Kappa: 0.219, 0.298, 0.244, respectively; p=0.743) and a moderate predictive performance, (area under the curve [AUC]=0.686, 0.665 and 0.716, respectively; p=0.048), with the D:A:D equation being the most accurate. Atherosclerosis was demonstrated in a significant proportion of subjects with low predicted CVD risk by all three algorithms (16.3%, 17.2%, 17.2%, respectively; p=0.743). In patients with an estimated low CVD risk atherosclerosis was associated with older age (p=0.012) and low CD4 counts (p=0.021). A model was developed to adjust the D:A:D equation; a significant increase in accuracy was obtained when CD4 counts and low-grade albuminuria were included (AUC=0.772; p<0.001). Conclusion: The D:A:D equation overperforms Framingham and SCORE in HIV patients. However, all three equations underestimate the presence of subclinical atherosclerosis in this population. The accuracy of the D:A:D equation improves when CD4 counts and low-grade albuminuria are incorporated into the equation. © The European Society of Cardiology 2012.


Guinea J.,Complutense University of Madrid | Guinea J.,Institute Investigacion Sanitaria Del Hospital Gregorio Maranon | Guinea J.,CIBER ISCIII | Zaragoza O.,Institute Salud Carlos III | And 9 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2014

We report the molecular identifications and antifungal susceptibilities of the isolates causing fungemia collected in the CANDIPOP population-based study conducted in 29 Spanish hospitals. A total of 781 isolates (from 767 patients, 14 of them having mixed fungemia) were collected. The species found most frequently were Candida albicans (44.6%), Candida parapsilosis (24.5%), Candida glabrata (13.2%), Candida tropicalis (7.6%), Candida krusei (1.9%), Candida guilliermondii (1.7%), and Candida lusitaniae (1.3%). Other Candida and non-Candida species accounted for approximately 5% of the isolates. The presence of cryptic species was low. Compared to findings of previous studies conducted in Spain, the frequency of C. glabrata has increased. Antifungal susceptibility testing was performed by using EUCAST and CLSI M27-A3 reference procedures; the two methods were comparable. The rate of fluconazole-susceptible isolates was 80%, which appears to be a decrease compared to findings of previous studies, explained mainly by the higher frequency of C. glabrata. Using the species-specific breakpoints and epidemiological cutoff values, the rate of voriconazole and posaconazole in vitro resistance was low (<2%). In the case of C. tropicalis, using the EUCAST procedure, the rate of azole resistance was around 20%. There was a correlation between the previous use of azoles and the presence of fluconazole-resistant isolates. Resistance to echinocandins was very rare (2%), and resistance to amphotericin B also was very uncommon. The sequencing of the hot spot (HS) regions from FKS1 or FKS2 genes in echi-nocandin-resistant isolates revealed previously described point mutations. The decrease in the susceptibility to fluconazole in Spanish isolates should be closely monitored in future studies. Copyright © 2014, American Society for Microbiology. All Rights Reserved.


Valerio M.,Hospital General Universitario Gregorio Maranon | Valerio M.,Institute Investigacion Sanitaria Del Hospital Gregorio Maranon | Rodriguez-Gonzalez C.G.,Institute Investigacion Sanitaria Del Hospital Gregorio Maranon | Rodriguez-Gonzalez C.G.,Hospital General Universitario Gregorio Maranon | And 10 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2014

Objectives: To assess the quality of antifungal use, to propose a point score for this evaluation and to estimate the potential economic savings of an antifungal stewardship programme. Methods: From December 2010 to January 2011, we identified 100 adult inpatients receiving systemic antifungals. Antifungal use was evaluated by means of a predefined score that considered indication, drug selection, dosage, adjustments after microbiology results, switching to an oral agent and length of treatment. Total antifungal prescriptions [in defined daily doses (DDDs) and days of therapy (DOTs)] and potential cost savings were calculated. Results: Overall, 43% of prescriptions came from medical departments, 25% from haematology/oncology and 17% from intensive care units. The main reasons for starting antifungals were empirical (42%), pre-emptive (20%) and targeted treatment (20%). Antifungals were unnecessary in 16% of cases. Inadequacies in other aspects of antifungal prescription were: drug selection, 31%; dosing, 16%; no switch from intravenous to oral administration, 20%; no adjustment after microbiological results, 35%; and length of therapy, 27%. The number of antifungal DDDs per 1000 patient-days was 65.1. The total number of DOTs was 1556, which added a direct cost of €219364. Only 51.3% of DOTs were considered optimal. The potential estimated savings would be €50536. Conclusions: Major efforts should be made to improve the selection and duration of antifungal therapy. Our study demonstrated the potential cost savings that could be achieved by optimizing antifungal therapy. A stewardship programme should include an instrument to objectively evaluate the adequacy of antifungal use. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

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