Efectividad de los antivirales de acción directa de segunda generación en el tratamiento de la hepatitis C crónica / Effectiveness of second-generation direct-acting antivirals in chronic hepatitis C

Fundamento: Los antivirales de acción directa de segunda generación (AAD) han demostrado porcentajes elevados de respuesta viral sostenida (RVS) en el tratamiento de la hepatitis C crónica en ensayos clínicos. Este estudio tiene como objetivo estimar la efectividad de los AAD en el tratamiento de esta enfermedad. Material y métodos: Se estudiaron pacientes monoinfectados por el virus de la hepatitis C (VHC) y coinfectados por VHC y virus de la inmunodeficiencia humana (VIH) que iniciaron tratamientos libres de interferón con AAD durante 2015. La RVS se definió como una carga viral indetectable a las 12 semanas de finalizar el tratamiento, y fue el indicador principal de efectividad. Resultados: Se incluyeron 293 pacientes, 52 (17,7%) coinfectados por VIH. Los genotipos VHC más prevalentes fueron el 1b en monoinfectados (41,5%) y 1a en coinfectados (40,4%). La proporción de cirróticos fue superior en la población coinfectada (69,2% vs 41,1%; p<0,0001), en su mayoría Child-Pugh A. La cifra global de RVS fue del 96,9% (284/293) en un análisis por intención de tratar (IC 95%: 94,9-98,9%), siendo 4 los pacientes con fracaso virológico. Tanto pacientes naïve como pretratados tuvieron RVS superior al 95%, y en la mayoría de subgrupos establecidos según la presencia o no de cirrosis, la coinfección VIH y el genotipo, la efectividad se situó próxima o por encima del 90%. Conclusiones: Los AAD presentan una efectividad elevada, igual o superior a la descrita en los ensayos clínicos, e incluso en subpoblaciones difíciles de tratar (AU)

Background: Second-generation direct-acting antivirals (DAA) have shown high sustained virologic response (SVR) for the treatment of chronic hepatitis C in clinical trials. The objective of this study is to estimate DAA effectiveness in treatment of this disease. Methods: Hepatitis C virus (HCV) monoinfected patients and HCV-human immunodeficiency virus (HIV) coinfected patients who started interferon-free DAA based regimens during 2015 were included. The primary effectiveness outcome was SVR, defined as an undetectable viral load 12 weeks after the end of treatment. Results: A total of 293 patients were enrolled, and 52 (17.7%) were HIV coinfected. HCV 1b genotype was the most prevalent in monoinfected patients (41.5%) and 1a in HIV coinfected patients (40.4%). The proportion of cirrhosis was higher among HIV coinfected patients (69.2% vs 41.1%; p<0.0001), mostly Child-Pugh A. SVR was achieved by 96.9% of patients (284/293), in an intention-to-treat analysis (CI 95%: 94.9- 98.9), in which just 4 people had virologic failure. Both naïve and pretreated patients had SVR higher than 95%, and in most of subgroups, according to the presence of cirrhosis, HIV coinfection and HVC genotype, effectiveness rates were near or above 90%. Conclusions: DAA are highly effective, with similar or higher rates of SVR than that found in clinical trials, and even among difficult to treat populations (AU)

Diagnóstico tardío de la infección por el virus de la inmunodeficiencia humana: oportunidades diagnósticas perdidas / Late diagnosis of HIV infection: missed diagnostic opportunities

Fundamento: Analizar el porcentaje de pacientes con diagnóstico tardío (DT) de infección por VIH, sus factores de riesgo y las oportunidades perdidas para un diagnóstico más precoz. Material y métodos: Se incluyó a 165 pacientes diagnosticados de infección por VIH entre 2009 y 2013 en Navarra. Mediante regresión logística se estudiaron los factores asociados con DT (CD4 <350 células/mm3 o enfermedad definitoria de sida al diagnóstico). Se analizó la presencia de factores de riesgo e indicadores clínicos de una posible infección por VIH en los 5 años previos al diagnóstico. Resultados: La prevalencia global de DT fue del 55% (90/165). Este porcentaje fue mayor en los pacientes inmigrantes que en los españoles, y en aquellos sin serología realizada previamente. Se observó una interacción entre la edad y el origen del paciente. En los españoles el riesgo de DT aumentó con la edad a partir de los 40 años (OR: 3,72; IC95%: 1,52-9,12) pero esto no ocurrió en los inmigrantes. De los 132 pacientes con atención médica en los años previos al diagnóstico, 20 (15%) tenían factores de riesgo clásicos documentados en la historia, 14 (11%) procedían de regiones con alta prevalencia de VIH y 46 (35%) habían presentado indicadores clínicos sin la realización de la serología. Conclusiones: A pesar de los múltiples contactos con nuestro sistema sanitario, más de la mitad de los nuevos diagnósticos de infección por VIH se realizan tarde. Es necesario una mayor atención a los signos clínicos de la infección y, sobre todo, una mejor valoración del riesgo en pacientes asintomáticos (AU)

Background: To analyse the percentage of patients with a late diagnosis (LD) of HIV infection, their risk factors and the missed opportunities for an earlier diagnosis. Methods: One hundred and sixty-five patients diagnosed with HIV infection in Navarre between 2009 and 2013 were included. Logistic regression was used to study the factors associated with LD (CD4 <350 cells/ mm3 or AIDS defining disease at diagnosis). The presence of risk factors and clinical indicators of possible HIV infection in the 5 years preceding the diagnosis were analyzed. Results: The global prevalence of LD was 55% (90/165). This percentage was greater in immigrant patients than in Spanish patients, and in those without previous serology tests. An interaction was observed between the age and origin of patients. In Spaniards the risk of LD rose with age after 40 years (OR: 3.72; 95%CI: 1.52-9.12) but this did not occur in immigrant patients. Of the 132 patients who had received medical care in the years prior to diagnosis, 20 (15%) had classical risk factors recorded in their history, 14 (11%) proceeded from regions with a high prevalence of HIV, and 46 (35%) had presented clinical indicators without a serology test being realized. Conclusions: In spite of multiple contacts with our health system, over half of the new cases of HIV infection are diagnosed late. Greater attention to clinical signs is needed and, above all, a better evaluation of the risk in asymptomatic patients (AU)

Reconocimiento profesional a médicos y médicas / Professional recognition of female and male doctors

Antecedentes y objetivo: Los premios a la excelencia del Colegio Oficial de Médicos de Barcelona (COMB) fueron instituidos en 2004 para reconocer la excelencia en el ejercicio profesional. Los premiados son elegidos anualmente por jurados nombrados por la junta de gobierno, cuyos miembros proponen médicos que en su opinión tienen un comportamiento profesional y humano ejemplar. Sujetos y métodos: Hemos analizado el número de médicos y médicas que han obtenido este reconocimiento y la relación entre el número de varones y mujeres premiados con la distribución por géneros en los jurados. Asimismo se han comparado las edades de médicos y médicas premiados y la de colegiados y colegiadas de más de 45 años. Resultados: La relación de varones y mujeres entre los premiados fue de 2,7/1 (rango: 1,2/1 para los premiados en Atención Primaria y 6/1 en el apartado Investigación), con una correlación directa no estadísticamente significativa entre la relación varones/mujeres premiados y jurados. La relación entre varones y mujeres colegiados con más de 45 años fue de 1,4/1, mientras que en los premiados fue de 2,7/1. En los últimos 4 años ha incrementado la proporción de mujeres en los jurados y de forma paralela ha aumentado el número de médicas premiadas. Conclusión: El predomino de varones entre los premiados parece relacionarse con la mayor proporción de varones en la composición de los jurados (AU)

Precedents and aim: The awards for the excellence of the Official College of Physicians of Barcelona (COMB) were instituted in 2004 to recognize the excellence of the professional exercise. The winners are yearly chosen by juries appointed by the board of government, whose members propose for the award doctors who, in their opinion, have an exemplary professional and human behaviour. Subjects and methods: The number of male and female doctors who have obtained this recognition has been analysed in relation with the sex distribution in the juries. Likewise it has been compared the ratios men-to-women of those who have been rewarded and this ratio among physicians of more than 45 years. Results: Between the awarded physicians the ratio men-to-women was of 2.7/1 (range, from 1.2/1 for awardees in primary care to 6/1 in research). The men-to-women ratio among those who were awarded was in parallel to the man-to-women ratios of the juries. The ratio between men and women among members of the COMB of more than 45 years was 1.4/1, whereas in those who were awarded it was of 2.7/1. The increase in the proportion of women in the juries in the last four years has been followed by an increase in the number of female physicians awarded. Conclusion: This data demonstrates that the predominance of male doctors among those who were awarded does not depend so much on the age factor, but basically on the proportion of male and female doctors in the juries (AU)

Professional recognition of female and male doctors.

PRECEDENTS AND AIM: The awards for the excellence of the Official College of Physicians of Barcelona (COMB) were instituted in 2004 to recognize the excellence of the professional exercise. The winners are yearly chosen by juries appointed by the board of government, whose members propose for the award doctors who, in their opinion, have an exemplary professional and human behaviour. SUBJECTS AND METHODS: The number of male and female doctors who have obtained this recognition has been analysed in relation with the sex distribution in the juries. Likewise it has been compared the ratios men-to-women of those who have been rewarded and this ratio among physicians of more than 45 years. RESULTS: Between the awarded physicians the ratio men-to-women was of 2.7/1 (range, from 1.2/1 for awardees in primary care to 6/1 in research). The men-to-women ratio among those who were awarded was in parallel to the man-to-women ratios of the juries. The ratio between men and women among members of the COMB of more than 45 years was 1.4/1, whereas in those who were awarded it was of 2.7/1. The increase in the proportion of women in the juries in the last four years has been followed by an increase in the number of female physicians awarded. CONCLUSION: This data demonstrates that the predominance of male doctors among those who were awarded does not depend so much on the age factor, but basically on the proportion of male and female doctors in the juries.

[Late diagnosis of HIV infection: missed diagnostic opportunities]. / Diagnóstico tardío de la infección por el virus de la inmunodeficiencia humana: oportunidades diagnósticas perdidas.

BACKGROUND: To analyse the percentage of patients with a late diagnosis (LD) of HIV infection, their risk factors and the missed opportunities for an earlier diagnosis. METHODS: One hundred and sixty-five patients diagnosed with HIV infection in Navarre between 2009 and 2113 were included. Logistic regression was used to study the factors associated with LD (CD4 < 350 cells/mm3 or AIDS defining disease at diagnosis). The presence of risk factors and clinical indicators of possible HIV infection in the 5 years preceding the diagnosis were analyzed. RESULTS: The global prevalence of LD was 55% (90/165). This percentage was greater in immigrant patients than in Spanish patients, and in those without previous serology tests. An interaction was observed between the age and origin of patients. In Spaniards the risk of LD rose with age after 40 years (OR: 3.72; 95%CI: 1.52-9.12) but this did not occur in immigrant patients. Of the 132 patients who had received medical care in the years prior to diagnosis, 20 (15%) had classical risk factors recorded in their history, 14 (11%) proceeded from regions with a high prevalence of HIV, and 46 (35%) had presented clinical indicators (only 24 of them 1 year before diagnosis) without a serology test being realized. CONCLUSIONS: In spite of multiple contacts with our health system, over half of the new cases of HIV infection are diagnosed late. Greater attention to clinical signs is needed and, above all, a better evaluation of the risk in asymptomatic patients.

Histopathological evidence of antagonistic effects of tributyltin on benzo[a]pyrene toxicity in the Arctic charr (Salvelinus alpinus).

We previously reported that long-term (54 days), repeated intraperitoneal exposure to low doses of tributyltin (TBT; 0.3 mg/kg) inhibited the metabolic activation of co-administered benzo[a]pyrene (BaP; 3 mg/kg) in the Arctic charr (Salvelinus alpinus); BaP, in turn, stimulated the metabolism and/or excretion of TBT. Here, we report the results of histopathological examinations of liver, kidney and pseudobranch tissue samples originating from these same fish. The results revealed higher lesion incidences at all sampling time points (Days 8, 32 and 56) among BaP-exposed fish compared with fish exposed to either TBT alone or combined with BaP. The severity of lesions like necrosis was also higher in BaP-exposed fish. Moreover, hepatic basophilic foci were observed exclusively in fish exposed to BaP alone. Together, these results provide new evidences that TBT can antagonize BaP toxicity in fish exposed to both pollutants under controlled laboratory conditions. In contrast, BaP does not appear to provide protection against TBT toxicity.

¿Qué hacer cuando el paciente es un colega? Dos años de experiencia del Programa de Atención Integral al Médico Enfermo (PAIME) / What to do when your patient is a colleague? two years of experience in the program of attending sich doctors

Este trabajo expone las razones que han motivado la creación del programa PAIMM por parte de los Colegios de Médicos de Cataluña y del Departamento de Sanidad y Seguridad Social de la Generalitat. Los problemas de los profesionales de la sanidad y sobre todo de los médicos, que padecen trastornos psíquicos y adictivos para acudir al sistema sanitario a recibir el tratamiento adecuado, son varios y diversos, pero la falta de confidencialidad es el más importante. Se describen también las características del programa y de su Unidad de Tratamiento, con los últimos datos asistenciales (AU)

New method for the in vitro evaluation of dental alloy bonding systems.

STATEMENT OF PROBLEM: Bonding systems are used in some fixed prosthetic devices with base alloys. However, different studies of the same dental alloy bonding agents, under similar circumstances, have yielded disparate results in bond strength testing. PURPOSE: This study compared directly 2 dental alloy bonding systems through a "duel" type of confrontation, which basically is a 2-way tensile force test. MATERIAL AND METHODS: Ninety Wiron 88 base alloy cylinders (diameter of 8 mm length 15 mm) were sandblasted on both sides with Al(2)0(3) powder (particle size 50 microm) during 10 seconds at an approximate distance of 5 mm, at an air pressure of 60 psi determined before sandblasting procedures. The surface of each cylinder was cleaned from Al(2)0(3) powder with a strong burst of oil-free air from a chairside air syringe. Thirty cylinders were randomly assigned to 1 of 3 groups for direct bond strength comparison: (1) Panavia 21 to Panavia EX, (2) Panavia 21 to Metabond, or (3) Panavia 21 to a combination of a resin bonding agent plus Panavia 21. Each group was composed of 10 specimens that used 3 cylinders for each specimen. Each side of the sample cylinder received the same quantity of cement and 1 cylinder at a time was bonded to it. Cylinder alignment was verified with a Boley gauge during luting procedures. The bonded 3-piece block was held together for 24 hours under a compressive force of 2 kg/cm(2) using a hydraulic press. Excess cement was removed with a brush, and the pertinent air sealant was applied to allow for autocuring of the cement. Specimens were later stored in water at room temperature for 48 hours before thermocycling procedures. Each specimen was thermocycled for 100 cycles with a 5-minute dwelling time in water at 4 degrees C and 60 degrees C. Specimens were subject to tensile force testing until debonding in 1 of the cylinders. RESULTS: The opposing pull duel test (OPDT) showed that the Panavia EX failed (40. 3 MPa) 10 of 10 duels against Panavia 21, whereas Panavia 21 failed (49.7 MPa) 9 of 10 duels against Metabond, and Panavia 1 failed (50. 1 MPa) 10 of 10 duels against Photobond+Panavia 21. ANOVA revealed significant differences (P <.05) between PAN-EX group and MET and PHB+P21 groups. However, no significant differences were found between MET and PHB+P21 groups. CONCLUSION: The opposing pull duel test was a valid method to directly compare bond strengths of 2 bonding systems to dental base alloys. There was a small dispersion of the values even though cement mixing and thickness variables were difficult to control. Duel tensile testing provides meaningful information on the superiority of one bonding system over another in this controlled environment.

In vivo formation of (+)-anti-benzo[a]pyrene diol-epoxide-plasma albumin adducts in fish.

Benzo[a]pyrene (BaP), a procarcinogenic polycyclic aromatic hydrocarbon (PAH), is bioactivated to BaP diol-epoxides (BPDEs) that can form adducts with DNA and blood proteins. We report here for the first time the in vivo formation of adducts between BPDE and plasma albumin (Alb) from two fish species experimentally exposed to BaP. Brook trout (Salvelinus fontinalis) received either a single i.p. dose (10 mg/kg) or two separate i.p. doses (25 mg/kg; 7 days apart) of BaP, and blood was collected 2 (single exposure) or 3 (multiple exposure) days post-treatment. Arctic charr (Salvelinus alpinus) received 10 i.p. doses (3 mg/kg; a single dose every 6 days), and blood was collected 2 days after the second, sixth, and 10th injections. BPDE-Alb adducts were measured by an improved HPLC/fluorescence method developed to detect and quantify BaP-tetrols released after acid hydrolysis of adducted Alb. HPLC/fluorescence chromatograms of Alb from BaP-treated fish revealed only BaP-tetrol I-1, thus indicating the formation of adducts exclusively via the (+)-anti-BPDE metabolite. Levels of (+)-anti-BPDE-Alb adduct ranged from 0.68 to 19.6 ng of tetrol I-1 per gram of Alb. Notably, adduct level was not related to BaP dose and there was no accumulation of adducts with repeated exposure, which may indicate a very short half-life (< 2 days) of plasma Alb in fish. The data suggest that BPDE-Alb adducts in fish could be useful as a non-destructive biomarker of recent exposure to bioactivated BaP.

[Brain lesions in patients with acquired immunodeficiency syndrome]. / Lesiones cerebrales en pacientes con síndrome de inmunodeficiencia adquirida.

During a period of 3 years 14 patients with AIDS and CNS focal lesions documented by CT scan were evaluated. All patients received empirical treatment against Toxoplasma. The aim of the study was to determine the prevalence of the different etiologies of the neurologic lesions as well as to evaluate the usefulness of routine cerebral biopsy before establishing empiric antitoxoplasma treatment in a population of AIDS patients with a high incidence of drug addiction. Eleven patients developed histologic and clinical criteria of cerebral toxoplasmosis, one patient presented progressive multifocal leukoencephalopathy, and in the remaining two patients the etiologic diagnosis could not be established. Only one patient presented multiple etiologic lesions and in no cases the presence of mycobacteria or fungi could be demonstrated in the cerebral tissue. The overall percentage of responses to the empiric antitoxoplasma treatment was 42%. This percentage increased to 54% if patients with coma were not included in the analysis. Cumulated mortality of the entire group was 78.5%. It is concluded: 1) the predominance of Toxoplasma gondii as a cause of cerebral lesions in our AIDS population; 2) the acceptable percentage of response to empiric antitoxoplasma treatment in non-comatose patients, and 3) the high overall mortality rate in these patients. It is therefore suggested that routine cerebral biopsies will not be justified as initial diagnostic approach in HIV positive patients with focal CNS lesions.

[Mycosis fungoides associated with HIV infection]. / Micosis fungoide asociada a infección por VIH.

The increasing number of cases of HIV-infections made the pathology association wider. Between these pathologies, tumors and lymphoid neoplasias are the most frequent. Large series showed the association between B-cell non-hodgkin lymphomas, and HIV infection, but only exceptional cases of T-cell lymphomas were found. We present a case of T-cell cutaneous lymphoma (mycosis fungoides) in a patient with HIV-infection owing to the fact that very few: cases have been reported, the causal relationship is still unknown.

[Infectious complications in the orthoptic liver transplant]. / Complicaciones infecciosas del trasplante hepático ortotópico.

Orthotopic liver transplantation is a therapeutic option for selected patients with end-stage liver disease. Among the complications of orthotopic liver transplantation infectious problems are a major cause of mortality. In this report the different types of infection following orthotopic liver transplantation are reviewed. In addition, currently available data regarding to transmission of infectious agents from organ donor to transplant recipient are reported.