Carlos Sánchez-Piedra

Modeling the Probability of Sustained Virological Response to Therapy with Pegylated Interferon plus Ribavirin in Patients Coinfected with Hepatitis C Virus and HIV

BACKGROUND A single-nucleotide polymorphism (SNP) near the IL28B gene (rs12979860) strongly predicts sustained virological response to pegylated interferon plus ribavirin (pegIFN-RBV) treatment for chronic hepatitis C virus (HCV) infection. Given that therapy is poorly tolerated and rates of response are lower in patients coinfected with HCV and human immunodeficiency virus (HIV), the recognition of predictors of response is a high priority in this population. METHODS A baseline noninvasive index was derived on the basis of the probability of achieving sustained virological response in a group of 159 HIV-HCV-coinfected patients treated at one clinic in Spain. The index was then validated using data from a separate cohort of 86 coinfected individuals. Only individuals who had completed a course of pegIFN-RBV therapy and had validated outcomes were considered. RESULTS The final score included 4 variables: 2 host-related variables (IL28B SNP rs12979860 and liver stiffness) and 2 HCV-related variables (genotype and viral load). The area under the receiver operating characteristic curve was 0.89 in the derivation group and 0.85 in the validation group. CONCLUSIONS The probability of achieving sustained virological response with pegIFN-RBV therapy in HIV-HCV-coinfected patients can be reliably estimated prior to initiation of therapy using an index that includes 4 noninvasive parameters.

Incidence of liver cirrhosis in HIV-infected patients with chronic hepatitis B or C in the era of highly active antiretroviral therapy.

BACKGROUND Longitudinal assessment of liver fibrosis with transient elastometry (TE) in patients with chronic viral hepatitis is becoming routine clinical practice in many clinics, as this procedure is non-invasive, easy to perform and relatively inexpensive, allowing early detection of cirrhosis. Herein, we examine the incidence of cirrhosis, using TE assessment, in HIV-infected individuals with chronic hepatitis B or C receiving highly active antiretroviral therapy (HAART). METHODS A longitudinal study was performed on a cohort of HIV-infected patients with chronic hepatitis B or C who were followed since 2004 at Hospital Carlos III (Madrid, Spain) with periodic TE assessments. The primary outcome was the development of cirrhosis, defined as liver stiffness >12.5 KPa. RESULTS A total of 508 HIV-infected patients were examined, of whom 54 developed liver cirrhosis during a mean ±(SD) follow-up of 2.6 ±1.0 years (overall incidence was 41.13 cases per 1,000 person-years). The risk of developing cirrhosis was significantly higher in 297 HCV-RNA-positive patients (either untreated or non-responders to hepatitis C therapy) compared with 55 patients who had cleared HCV with therapy (odds ratio 3.73, 95% confidence interval 1.06-13.17; P=0.04). By contrast, the risk of developing cirrhosis was low and similar in 24 HIV-HBV-coinfected patients under long-term suppressive HBV therapy (mainly tenofovir disoproxil fumarate), 132 HIV-infected patients without chronic liver disease and those who had cleared HCV with therapy. CONCLUSIONS Development of liver cirrhosis in HIV-infected individuals in the HAART era is mainly associated with active HCV coinfection. The risk of developing cirrhosis is negligible in patients who cleared HCV with therapy, as well as in HIV-HBV-coinfected patients on long-term suppressive tenofovir disoproxil fumarate therapy.

Soluble markers of inflammation are associated with Framingham scores in HIV-infected patients on suppressive antiretroviral therapy

OBJECTIVE To evaluate the association between biomarkers of inflammation and endothelial dysfunction and Framingham scores (FS) for risk of coronary heart disease (FS-CHD), stroke (FS-Stroke) or any cardiovascular event (FS-CVE) in HIV-infected on suppressive highly active antiretroviral therapy (HAART). METHODS A cross-sectional study was conducted in 73 HIV-infected patients and 23 healthy controls. Inflammatory molecules and endothelial dysfunction markers were measured using a multiplex immunoassay (plasminogen activator inhibitor type 1 (PAI-1), soluble TNF receptor type 1 (sTNF-R1), soluble CD40 ligand (sCD40L), soluble E-selectin (sE-selectin), soluble P-selectin (sP-selectin), soluble intercellular adhesion molecules (sICAM-1) and soluble vascular cell adhesion molecule (sVCAM-1). Outcome variables were FS-CHD ≥10%, FS-Stroke ≥5% and FS-CVE ≥10%. RESULTS Significant differences (p < 0.05) were found comparing controls and HIV patients for PAI-1 (5.4 vs. 13.5 ng/dL), sTNF-R1 (0.85 vs. 1.09 ng/dL), sICAM-1 (529 vs. 858 ng/dL), sE-selectin (73.7 vs. 120 ng/dL), sP-selectin (676 vs. 1511 ng/dL) sCD40L (76 vs. 307 ng/dL), FS-CHD (4% vs. 7.8% L), FS-Stroke (2% vs. 2.8%) and FS-CVE (5% vs. 11%). In HIV-infected patients, the adjusted logistic regression analysis revealed that sTNF-R1 levels were significantly associated with increased FS-CHD>10% (OR: 11.51 (95% CI: 1.14; 115.84); p = 0.038) and FS-CVE (OR: 12.41 (95% CI: 1.25; 123.23); p = 0.031). CONCLUSIONS HIV-infected patients show higher levels of soluble inflammatory and endothelial dysfunction markers than controls and have a two-fold increased FS of presenting coronary heart disease, stroke or cardiovascular events at 10 years. Furthermore, sTNF-R1 displayed the best association with FS of coronary heart disease and any cardiovascular event in our patients.

SJÖGREN-SER: Registro nacional de pacientes con síndrome de Sjögren primario de la Sociedad Española de Reumatología: objetivos y metodología

OBJECTIVE To describe the objectives and methods of the Spanish Society of Rheumatology primary Sjögren syndrome (pSS) registry (SJOGREN-SER) METHODS: This is a multicenter descriptive transversal study of a cohort of pSS patients fulfilling European/American consensus criteria collected from Rheumatology clinics all over Spain. Patients were included by randomisation from an anonymised list provided by every department. Data were collected by reviewing clinical records and an interviewing the patients. Two hundred and ninety eight variables were investigated: epidemiological, clinical, serological characteristics, treatments and complications. Informed consent was obtained and local ethics committees approved the study. Variables were analysed by descriptive statistical methods, using means, medians, and rates, with their deviations and interquartile ranges (p25-p75). RESULTS A total of 3 rheumatology departments participated in the registry. A total of 437 patients were included. And 95% of them were women, with a median age of 58. Median age at pSS s diagnosis was 50 years. Dryness symptoms (95%) were the most frequent complaint and anti-Ro/SS-A were present in 94% of the cases. Only 27% of the patients fulfilled the new 2012 SICCA-ACR classification criteria. CONCLUSIONS SJOGREN-SER has been designed in order to characterize a representative pSS Spanish cohort, in clinical daily practice, to analyze the magnitude and distribution of its manifestations, activity, accumulated damage and therapeutic management of the disease. This will allow broadening the knowledge of this disease and plan strategies of action in pSS.

Comorbidities in patients with Primary Sjögren's Syndrome and Systemic Lupus Erythematosus: A comparative registries‐based study

To compare the prevalence of the main comorbidities in 2 large cohorts of patients with primary Sjögrens syndrome (SS) and systemic lupus erythematosus (SLE), with a focus on cardiovascular (CV) diseases.

Factors associated with severe dry eye in primary Sjögren’s syndrome diagnosed patients

IntroductionPrimary Sjögren’s syndrome (pSS) is an autoimmune disease, characterized by lymphocytic infiltration of exocrine glands and other organs, resulting in dry eye, dry mouth and extraglandular systemic findings.ObjectiveTo explore the association of severe or very severe dry eye with extraocular involvement in patients diagnosed with primary Sjögren’s syndrome.MethodsSJOGRENSER registry is a multicenter cross-sectional study of pSS patients. For the construction of our main variable, severe/very severe dry eye, we used those variables that represented a degree 3–4 of severity according to the 2007 Dry Eye Workshop classification. First, bivariate logistic regression models were used to identify the effect of each independent variable on severe/very severe dry eye. Secondly, multivariate analysis using regression model was used to establish the independent effect of patient characteristics.ResultsFour hundred and thirty-seven patients were included in SJOGRENSER registry; 94% of the patients complained of dry eye and 16% developed corneal ulcer. Schirmer’s test was pathological in 92% of the patients; 378 patients presented severe/very severe dry eye. Inflammatory articular involvement was significantly more frequent in patients with severe/very severe dry eye than in those without severe/very severe dry eye (82.5 vs 69.5%, p = 0,028). Inflammatory joint involvement was associated with severe/very severe dry eye in the multivariate analysis, OR 2.079 (95% CI 1.096–3.941).ConclusionSevere or very severe dry eye is associated with the presence of inflammatory joint involvement in patients with pSS. These results suggest that a directed anamnesis including systemic comorbidities, such as the presence of inflammatory joint involvement or dry mouth in patients with dry eye, would be useful to suspect a pSS.

Biodegradable stents for the treatment of refractory or recurrent benign esophageal stenosis

ABSTRACT Introduction: Esophageal stents are used for the treatment of refractory and recurrent dyphagias. In 2007, esophageal biodegradable stents (EBS) were authorised as an alternative to existing metal and plastic stents in Europe. The advantages claimed for EBS are fewer complications concerning tissue ingrowth, stent migration and stent removal. Areas covered: We performed a systematic review to evaluate the efficacy and safety of EBS compared to fully-covered self-expanding metal stents, self-expanding plastic stents, and esophageal dilation for the treatment of refractory or recurrent benign esophageal stenosis. Three comparative studies (one randomized controlled trial and two cohort studies) were assessed. The studies used different inclusion criteria, had a very small (sample) size and the quality of the evidence was very low. Expert commentary: The current evidence is insufficient to determine the relative efficacy or safety of esophageal biodegradable stents. The results of this systematic review should be updated once new evidence is available.

Supervivencia de pacientes con insuficiencia cardiaca en atención primaria

Resumen Objetivo Describir la supervivencia de los pacientes con insuficiencia cardiaca (IC) con seguimiento en atención primaria (AP) y analizar el efecto del sexo, edad, factores clínicos, de utilización de servicios y nivel de renta, en la supervivencia. Diseño Estudio observacional longitudinal de una cohorte retrospectiva de pacientes a partir de la historia clínica electrónica. Emplazamiento Área 7 de AP de la Comunidad de Madrid. Participantes Pacientes mayores de 24 años con una consulta en AP en el año 2006. Mediciones principales Casos incidentes de IC desde 2006 a 2010 o hasta su fallecimiento. Análisis de supervivencia de Kaplan-Meier y de regresión multivariante de riesgos proporcionales de Cox. Resultados Se identificaron 3.061 pacientes en una cohorte de 227.984. Su supervivencia fue del 65% a los 5 años. Fallecieron 519 pacientes con una supervivencia media de 49 meses. Los factores asociados a mayor riesgo de mortalidad fueron la edad (HR = 1,04; 1,03-1,05) y tener diagnóstico de cardiopatía isquémica (HR = 1,45; 1,15-1,78) o de diabetes (HR = 1,52; 1,17-1,95). Los factores con un efecto protector fueron ser mujer (HR = 0,72; 0,59-0,86), no pensionista (HR = 0,43; 0,23-0,84), haber recibido la vacunación de la gripe anualmente (HR = 0,01; 0,00-0,06), tener prescritos hipolipidemiantes (HR = 0,78; 0,61-0,99) o IECA (HR = 0,73; 0,60-0,88), así como que se le hubieran solicitado analíticas (HR = 0,98; 0,95-1), radiografías (HR = 0,81; 0,74-0,88) y electrocardiogramas (HR = 0,90; 0,81-0,99) en AP. Conclusiones Los datos de los pacientes con IC seguidos en AP indican que su supervivencia es mejor que la obtenida en otros países, apoyando el argumento de la mejor evolución de la IC en los países mediterráneos.

Variabilidad en los hospitales de día de Reumatología en España: proyecto VALORA

OBJECTIVE To describe the variability of the day care hospital units (DCHUs) of Rheumatology in Spain, in terms of structural resources and operating processes. MATERIAL AND METHODS Multicenter descriptive study with data from a self-completed questionnaire of DCHUs self-assessment based on DCHUs quality standards of the Spanish Society of Rheumatology. Structural resources and operating processes were analyzed and stratified by hospital complexity (regional, general, major and complex). Variability was determined using the coefficient of variation (CV) of the variable with clinical relevance that presented statistically significant differences when was compared by centers. RESULTS A total of 89 hospitals (16 autonomous regions and Melilla) were included in the analysis. 11.2% of hospitals are regional, 22,5% general, 27%, major and 39,3% complex. A total of 92% of DCHUs were polyvalent. The number of treatments applied, the coordination between DCHUs and hospital pharmacy and the post graduate training process were the variables that showed statistically significant differences depending on the complexity of hospital. The highest rate of rheumatologic treatments was found in complex hospitals (2.97 per 1,000 population), and the lowest in general hospitals (2.01 per 1,000 population). The CV was 0.88 in major hospitals; 0.86 in regional; 0.76 in general, and 0.72 in the complex. CONCLUSIONS there was variability in the number of treatments delivered in DCHUs, being greater in major hospitals and then in regional centers. Nonetheless, the variability in terms of structure and function does not seem due to differences in center complexity.

Objetivos y metodología de la fase iii de BIOBADASER

OBJECTIVE Describe the objectives, methods and results of the first year of the new version of the Spanish registry of adverse events involving biological therapies and synthetic drugs with an identifiable target in rheumatic diseases (BIOBADASER III). METHODOLOGY Multicenter prospective registry of patients with rheumatic inflammatory diseases being treated with biological drugs or synthetic drugs with an identifiable target in rheumatology departments in Spain. The main objective of BIOBADASER Phase III is the registry and analysis of adverse events; moreover, a secondary objective was added consisting of assessing the effectiveness by means of the registry of activity indexes. Patients in the registry are evaluated at least once every year and whenever they experience an adverse event or a change in treatment. The collection of data for phase iii began on 17 December 2015. RESULTS During the first year, 35 centers participated. The number of patients included in this new phase in December 2016 was 2,664. The mean age was 53.7 years and the median duration of treatment was 8.1 years. In all, 40.4% of the patients were diagnosed with rheumatoid arthritis. The most frequent adverse events were infections and infestations. CONCLUSIONS BIOBADASER Phase III has been launched to adapt to a changing pharmacological environment, with the introduction of biosimilars and small molecules in the treatment of rheumatic diseases. This new stage is adapted to the changes in the reporting of adverse events and now includes information related to activity scores.