[Emergency detection of HIV infection in patients consulting for conditions potentially related to occult infection: Initial results of the "Urgències VIHgila" program]. / Detección en urgencias de infección por VIH en pacientes que consultan por condiciones potencialmente relacionadas con infección oculta: Resultados iniciales del programa "Urgències VIHgila".

OBJECTIVE: To estimate the prevalence of unknown HIV infection in patients who consulted in hospital emergency services (ED) for conditions defined in the SEMES-GESIDA Consensus Document (DC), evaluate the efficiency of its im-plementation and investigate the efficiency of HIV serology determination in other conditions. METHODS: Results were reviewed in 10 Catalan EDs for 12 months (July-21-June-22) after implementing CD recommendations: request HIV serology in case of suspected sexually transmitted infection, chemsex, post-exposure prophylaxis (PEP), mononucleosis syndrome, community pneumonia (18-65 y-o) or herpes zoster (18-65 y-o). Other reasons for request were included. Prevalence (%) of global seropositivity and for each circumstance was calculated, with a 95% confidence interval (95%CI). The efficient strategy was considered if the lower limit of the CI95%>0.1%. RESULTS: A total of5,107 HIV serologies were performed: 2,847(56%) in situations specified in CD, and 2,266 (44%) in other 138 circumstances. Forty-eight unknown HIV infections were detected (prevalence=0.94%;95%CI=0.69-1.24). The prevalence was somewhat higher in DC requests (30 cas-es 1.12%) than the rest (18 cases 0.71%; p=0.16). The individualized prevalence of CD reasons ranged between 7.41% (95%CI=0.91-24.3) in chemsex and 0.42% 95%CI=0.14-0.98) in PPE, always efficient except herpes zoster (0.76%; CI95%=0.02-4.18). In other reasons, cases were detected in 12 circumstances, and in four the determination could be efficient: lymphopenia (10%;CI95%=0.25-44.5), fever with polyarthralgia-polyarthritis (7.41%;CI95% =0.91-24.3), behavioral alteration-confusion-encephalopathy (3.45%;95%CI=0.42-11.9) and fever of unknown origin (2.50%;95%CI=0.82-5.74). CONCLUSIONS: The determination of HIV serology in HES in the processes defined by DC SEMES-GESIDA is efficient. Some circumstances are identified that could be added to those previously contemplated to increase efficiency.

Secondary use of data extracted from a clinical information system to assess the adherence of tidal volume and its impact on outcomes.

OBJECTIVES: To extract data from clinical information systems to automatically calculate high-resolution quality indicators to assess adherence to recommendations for low tidal volume. DESIGN: We devised two indicators: the percentage of time under mechanical ventilation with excessive tidal volume (>8mL/kg predicted body weight) and the percentage of patients who received appropriate tidal volume (≤8mL/kg PBW) at least 80% of the time under mechanical ventilation. We developed an algorithm to automatically calculate these indicators from clinical information system data and analyzed associations between them and patients' characteristics and outcomes. SETTINGS: This study has been carried out in our 30-bed polyvalent intensive care unit between January 1, 2014 and November 30, 2019. PATIENTS: All patients admitted to intensive care unit ventilated >72h were included. INTERVENTION: Use data collected automatically from the clinical information systems to assess adherence to tidal volume recommendations and its outcomes. MAIN VARIABLES OF INTEREST: Mechanical ventilation days, ICU length of stay and mortality. RESULTS: Of all admitted patients, 340 met the inclusion criteria. Median percentage of time under mechanical ventilation with excessive tidal volume was 70% (23%-93%); only 22.3% of patients received appropriate tidal volume at least 80% of the time. Receiving appropriate tidal volume was associated with shorter duration of mechanical ventilation and intensive care unit stay. Patients receiving appropriate tidal volume were mostly male, younger, taller, and less severely ill. Adjusted intensive care unit mortality did not differ according to percentage of time with excessive tidal volume or to receiving appropriate tidal volume at least 80% of the time. CONCLUSIONS: Automatic calculation of process-of-care indicators from clinical information systems high-resolution data can provide an accurate and continuous measure of adherence to recommendations. Adherence to tidal volume recommendations was associated with shorter duration of mechanical ventilation and intensive care unit stay.

Secondary use of data extracted from a clinical information system to assess the adherence of tidal volume and its impact on outcomes / Uso secundario de los datos del Sistema de Información Clínica para evaluar la adherencia a las guías de práctica clínica respecto al volumen tidal y su impacto en los resultados

Objectives To extract data from clinical information systems to automatically calculate high-resolution quality indicators to assess adherence to recommendations for low tidal volume. Design We devised two indicators: the percentage of time under mechanical ventilation with excessive tidal volume (>8mL/kg predicted body weight) and the percentage of patients who received appropriate tidal volume (≤8mL/kg PBW) at least 80% of the time under mechanical ventilation. We developed an algorithm to automatically calculate these indicators from clinical information system data and analyzed associations between them and patients’ characteristics and outcomes. Settings This study has been carried out in our 30-bed polyvalent intensive care unit between January 1, 2014 and November 30, 2019. Patients All patients admitted to intensive care unit ventilated >72h were included. Intervention Use data collected automatically from the clinical information systems to assess adherence to tidal volume recommendations and its outcomes. Main variables of interest Mechanical ventilation days, ICU length of stay and mortality. Results Of all admitted patients, 340 met the inclusion criteria. Median percentage of time under mechanical ventilation with excessive tidal volume was 70% (23%–93%); only 22.3% of patients received appropriate tidal volume at least 80% of the time. Receiving appropriate tidal volume was associated with shorter duration of mechanical ventilation and intensive care unit stay. Patients receiving appropriate tidal volume were mostly male, younger, taller, and less severely ill. Adjusted intensive care unit mortality did not differ according to percentage of time with excessive tidal volume or to receiving appropriate tidal volume at least 80% of the time (AU)

Objetivos Extraer los datos del Sistema de Información Clínica para calcular automáticamente indicadores de calidad de alta resolución para evaluar la adherencia a las recomendaciones sobre el volumen tidal. Diseño Ideamos 2 indicadores: el porcentaje de tiempo en ventilación mecánica con volumen tidal excesivo (>8mL/kg peso ideal) y el porcentaje de pacientes con volumen tidal apropiado (≤8mL/kg peso ideal) al menos el 80% del tiempo en ventilación mecánica. Desarrollamos un algoritmo para calcular automáticamente dichos indicadores con los datos del Sistema de Información Clínica y analizamos su asociación con las características de los pacientes y su evolución. Ambiente El estudio se llevó a cabo en una unidad de cuidados intensivos polivalente de 30 camas desde el 1 enero 2014 hasta el 20 noviembre 2019. Pacientes Se incluyeron en el estudio todos los pacientes ingresados en la unidad de cuidados intensivos conectados a ventilación mecánica>72h. Intervención Usar los datos recogidos automáticamente desde el Sistema de Información Clínica para evaluar la adherencia a las recomendaciones del volumen tidal y sus resultados. Principales variables de interés Días de ventilación mecánica, días de estancia en la unidad de cuidados intensivos y mortalidad. Resultados De todos los pacientes ingresados, 340 cumplieron los criterios de inclusión. El tiempo medio de ventilación mecánica con volumen tidal excesivo fue 70% (23-93%); solo el 22,3% de los pacientes recibió un volumen tidal apropiado al menos el 80% del tiempo. Recibir un volumen tidal apropiado se asoció con menos días de ventilación mecánica y de estancia en la unidad de cuidados intensivos. Los pacientes que recibieron un volumen tidal apropiado fueron más frecuentemente hombres, más jóvenes, más altos y menos graves (AU)

Impact of Aspergillus spp. isolation in the first 24 hours of admission in critically ill patients with severe influenza virus pneumonia.

OBJECTIVE: To determine the incidence and impact of Aspergillus spp. isolation (AI) on ICU mortality in critically ill patients with severe influenza pneumonia during the first 24h of admission. DESIGN: Secondary analysis of an observational and prospective cohort study. SETTING: ICUs voluntary participating in the Spanish severe Influenza pneumonia registry, between June 2009 and June 2019. PATIENTS: Consecutive patients admitted to the ICU with diagnosis of severe influenza pneumonia, confirmed by real-time polymerase chain reaction. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Incidence of AI in respiratory samples. Demographic variables, comorbidities, need for mechanical ventilation and the presence of shock according at admission. Acute Physiology and Chronic Health Evaluation II (APACHE II) scale calculated on ICU admission. RESULTS: 3702 patients were analyzed in this study. AI incidence was 1.13% (n=42). Hematological malignancies (OR 4.39, 95% CI 1.92-10.04); HIV (OR 3.83, 95% CI 1.08-13.63), and other immunosuppression situations (OR 4.87, 95% CI 1.99-11.87) were factors independently associated with the presence of Aspergillus spp. The automatic CHAID decision tree showed that hematologic disease with an incidence of 3.3% was the most closely AI related variable. Hematological disease (OR 2.62 95% CI 1.95-3.51), immunosuppression (OR 2.05 95% CI 1.46-2.88) and AI (OR 3.24, 95% CI 1.60-6.53) were variables independently associated with ICU mortality. CONCLUSIONS: Empirical antifungal treatment in our population may only be justified in immunocompromised patients. In moderate-high risk cases, active search for Aspergillus spp. should be implemented.

Prior influenza vaccine is not a risk factor for bacterial coinfection in patients admitted to the ICU due to severe influenza.

OBJECTIVE: To determine whether the prior usage of the flu vaccine is a risk factor for bacterial co-infection in patients with severe influenza. DESIGN: This was a retrospective observational cohort study of subjects admitted to the ICU. A propensity score matching, and logistic regression adjusted for potential confounders were carried out to evaluate the association between prior influenza vaccination and bacterial co-infection. SETTINGS: 184 ICUs in Spain due to severe influenza. PATIENTS: Patients included in the Spanish prospective flu registry. INTERVENTIONS: Flu vaccine prior to the hospital admission. RESULTS: A total of 4175 subjects were included in the study. 489 (11.7%) received the flu vaccine prior to develop influenza infection. Prior vaccinated patients were older 71 [61-78], and predominantly male 65.4%, with at least one comorbid condition 88.5%. Prior vaccination was not associated with bacterial co-infection in the logistic regression model (OR: 1.017; 95%CI 0.803-1.288; p=0.885). After matching, the average treatment effect of prior influenza vaccine on bacterial co-infection was not statistically significant when assessed by propensity score matching (p=0.87), nearest neighbor matching (p=0.59) and inverse probability weighting (p=0.99). CONCLUSIONS: No association was identified between prior influenza vaccine and bacterial coinfection in patients admitted to the ICU due to severe influenza. Post influenza vaccination studies are necessary to continue evaluating the possible benefits.

The relationship between running distance and coaches' perception of team performance in professional soccer player during multiple seasons.

This study analyzed how the physical movement profile of soccer matches evolved throughout a season by assessing the variability of different metrics depending on the season phase. In addition, the evolution of running distances was investigated in the relation to the team performance based on the coaches' perception. Games from four consecutives Spanish LaLiga seasons (n = 1520) were recorded using an optical tracking system (i.e., ChyronHego). Total distance (TD), distance covered between 14 and 21 km h-1 (MIRD), 21-24 km h-1 (HIRD), and > 24 km h-1 (VHIRD) were analyzed, as well as the number of efforts between 21 and 24 km h-1 (Sp21) and > 24 km h-1 (Sp24). Seasons were divided into four phases (P): P1 (matches 1-10), P2 (11-19), P3 (20-29), and P4 (30-38). Linear mixed models revealed that soccer players covered significantly greater distances and completed a higher number of sprints in P2 and P3. Also, team performance evaluated by soccer coaches was positively related to TD, HIRD, VHIRD and Sp21 in P1. A negative relationship was observed between team performance and distance covered at speeds below 21 km h-1 in P2 and P3. Team performance was negatively related to TD, MIRD, and HIRD, and Sp21 in P4. As conclusion, the team performance perceived by coaches is related to the movement profile throughout a season, and it significantly influences the evolution of soccer players' movement profiles. Specifically, it seems that the players of the best teams have the best physical performance at the beginning of the season with respect to the rest of the phases.

Prior influenza vaccine is not a risk factor for bacterial coinfection in patients admitted to the ICU due to severe influenza.

OBJECTIVE: To determine whether the prior usage of the flu vaccine is a risk factor for bacterial co-infection in patients with severe influenza. DESIGN: This was a retrospective observational cohort study of subjects admitted to the ICU. A propensity score matching, and logistic regression adjusted for potential confounders were carried out to evaluate the association between prior influenza vaccination and bacterial co-infection. SETTINGS: 184 ICUs in Spain due to severe influenza. PATIENTS: Patients included in the Spanish prospective flu registry. INTERVENTIONS: Flu vaccine prior to the hospital admission. RESULTS: A total of 4175 subjects were included in the study. 489 (11.7%) received the flu vaccine prior to develop influenza infection. Prior vaccinated patients were older 71 [61-78], and predominantly male 65.4%, with at least one comorbid condition 88.5%. Prior vaccination was not associated with bacterial co-infection in the logistic regression model (OR: 1.017; 95%CI 0.803-1.288; p=0.885). After matching, the average treatment effect of prior influenza vaccine on bacterial co-infection was not statistically significant when assessed by propensity score matching (p=0.87), nearest neighbor matching (p=0.59) and inverse probability weighting (p=0.99). CONCLUSIONS: No association was identified between prior influenza vaccine and bacterial coinfection in patients admitted to the ICU due to severe influenza. Post influenza vaccination studies are necessary to continue evaluating the possible benefits.

Recommendations for the diagnosis and treatment of Clostridioides difficile infection: An official clinical practice guideline of the Spanish Society of Chemotherapy (SEQ), Spanish Society of Internal Medicine (SEMI) and the working group of Postoperative Infection of the Spanish Society of Anesthesia and Reanimation (SEDAR).

This document gathers the opinion of a multidisciplinary forum of experts on different aspects of the diagnosis and treatment of Clostridioides difficile infection (CDI) in Spain. It has been structured around a series of questions that the attendees considered relevant and in which a consensus opinion was reached. The main messages were as follows: CDI should be suspected in patients older than 2 years of age in the presence of diarrhea, paralytic ileus and unexplained leukocytosis, even in the absence of classical risk factors. With a few exceptions, a single stool sample is sufficient for diagnosis, which can be sent to the laboratory with or without transportation media for enteropathogenic bacteria. In the absence of diarrhoea, rectal swabs may be valid. The microbiology laboratory should include C. difficile among the pathogens routinely searched in patients with diarrhoea. Laboratory tests in different order and sequence schemes include GDH detection, presence of toxins, molecular tests and toxigenic culture. Immediate determination of sensitivity to drugs such as vancomycin, metronidazole or fidaxomycin is not required. The evolution of toxin persistence is not a suitable test for follow up. Laboratory diagnosis of CDI should be rapid and results reported and interpreted to clinicians immediately. In addition to the basic support of all diarrheic episodes, CDI treatment requires the suppression of antiperistaltic agents, proton pump inhibitors and antibiotics, where possible. Oral vancomycin and fidaxomycin are the antibacterials of choice in treatment, intravenous metronidazole being restricted for patients in whom the presence of the above drugs in the intestinal lumen cannot be assured. Fecal material transplantation is the treatment of choice for patients with multiple recurrences but uncertainties persist regarding its standardization and safety. Bezlotoxumab is a monoclonal antibody to C. difficile toxin B that should be administered to patients at high risk of recurrence. Surgery is becoming less and less necessary and prevention with vaccines is under research. Probiotics have so far not been shown to be therapeutically or preventively effective. The therapeutic strategy should be based, rather than on the number of episodes, on the severity of the episodes and on their potential to recur. Some data point to the efficacy of oral vancomycin prophylaxis in patients who reccur CDI when systemic antibiotics are required again.

Relationship between acute kidney injury and serum procalcitonin (PCT) concentration in critically ill patients with influenza infection / Relación entre disfunción renal aguda y valores séricos de procalcitonina en pacientes críticos con infección por gripe

INTRODUCTION: Serum procalcitonin (PCT) concentration could be increased in patients with renal dysfunction in the absence of bacterial infection. OBJECTIVE: To determine the interactions among serum renal biomarkers of acute kidney injury (AKI) and serum PCT concentration, in patients admitted to the intensive care unit (ICU) due to lung influenza infection. DESIGN: Secondary analysis of a prospective multicentre observational study. SETTING: 148 Spanish ICUs. PATIENTS: ICU patients admitted with influenza infection without bacterial co-infection. Clinical, laboratory and hemodynamic variables were recorded. AKI was classified as AKI I or II based on creatinine (Cr) concentrations (≥1.60-2.50mg/dL and Cr≥2.51-3.99mg/dL, respectively). Patients with chronic renal disease, receiving renal replacement treatment or with Cr>4mg/dL were excluded. Spearman's correlation, simple and multiple linear regression analysis were performed. INTERVENTIONS: None. RESULTS: Out of 663 patients included in the study, 52 (8.2%) and 10 (1.6%) developed AKI I and II, respectively. Patients with AKI were significantly older, had more comorbid conditions and were more severally ill. PCT concentrations were higher in patients with AKI (2.62 [0.60-10.0]ng/mL vs. 0.40 [0.13-1.20]ng/mL, p = 0.002). Weak correlations between Cr/PCT (rho=0.18) and Urea (U)/PCT (rho=0.19) were identified. Simple linear regression showed poor interaction between Cr/U and PCT concentrations (Cr R2=0.03 and U R2=0.018). Similar results were observed during multiple linear regression analysis (Cr R2=0.046 and U R2=0.013). CONCLUSIONS: Although PCT concentrations were slightly higher in patients with AKI, high PCT concentrations are not explained by AKI and could be warning sign of a potential bacterial infection

INTRODUCCIÓN: Los niveles de procalcitonina (PCT) pueden elevarse en pacientes con disfunción renal aún en ausencia de infección bacteriana. OBJETIVOS: Determinar la interacción entre los biomarcadores de disfunción renal aguda (AKI) y las concentraciones séricas de PCT en pacientes ingresados en cuidados intensivos (UCI) debido a infección por gripe. DISEÑO: Análisis secundario de un estudio prospectivo, multicéntrico observacional. Lugar: Ciento cuarenta y ocho UCI. PACIENTES: Con infección por gripe sin co-infección bacteriana. Se registraron las variables clínicas, de laboratorio y hemodinámicas. El nivel de AKI fue definido como AKI I y II basado en la creatinina (Cr) sérica (>1,60-2,50mg/dl y >2,51-3,99mg/dl), respectivamente. Pacientes con insuficiencia renal crónica, técnicas de reemplazo renal o Cr>4mg/dl fueron excluidos. El análisis estadístico se realizó mediante correlación de Spearman y regresión linear simple y múltiple. INTERVENCIONES: Ninguna. RESULTADOS: De los 663 pacientes incluidos, 52 (8,2%) y 10 (1,6%) desarrollaron AKI I y II, respectivamente. Pacientes con AKI fueron más añosos, presentaron más comorbilidades y mayor nivel de gravedad. Los niveles de PCT fueron mayores en pacientes con AKI (2,62 [0,60-10,0] ng/ml vs. 0,40 [0,13-1,20] ng/ml; p = 0,002). Se observaron correlaciones débiles entre Cr/PCT (rho=0,18) y PCT/U (rho=0,19). La regresión linear simple evidenció una pobre contribución tanto de Cr (R2=0,03) como de U (R2=0,018) sobre los niveles de PCT. Resultados similares fueron obtenidos con la regresión linear múltiple para Cr (R2=0,046) y U (R2=0,013). CONCLUSIONES: Aunque los valores de PCT pueden estar elevados en pacientes con AKI, altos niveles de PCT no pueden ser explicados por la disfunción renal y podrían ser un signo de alarma de una potencial infección bacteriana

Relationship between acute kidney injury and serum procalcitonin (PCT) concentration in critically ill patients with influenza infection.

INTRODUCTION: Serum procalcitonin (PCT) concentration could be increased in patients with renal dysfunction in the absence of bacterial infection. OBJECTIVE: To determine the interactions among serum renal biomarkers of acute kidney injury (AKI) and serum PCT concentration, in patients admitted to the intensive care unit (ICU) due to lung influenza infection. DESIGN: Secondary analysis of a prospective multicentre observational study. SETTING: 148 Spanish ICUs. PATIENTS: ICU patients admitted with influenza infection without bacterial co-infection. Clinical, laboratory and hemodynamic variables were recorded. AKI was classified as AKI I or II based on creatinine (Cr) concentrations (≥1.60-2.50mg/dL and Cr≥2.51-3.99mg/dL, respectively). Patients with chronic renal disease, receiving renal replacement treatment or with Cr>4mg/dL were excluded. Spearman's correlation, simple and multiple linear regression analysis were performed. INTERVENTIONS: None. RESULTS: Out of 663 patients included in the study, 52 (8.2%) and 10 (1.6%) developed AKI I and II, respectively. Patients with AKI were significantly older, had more comorbid conditions and were more severally ill. PCT concentrations were higher in patients with AKI (2.62 [0.60-10.0]ng/mL vs. 0.40 [0.13-1.20]ng/mL, p=0.002). Weak correlations between Cr/PCT (rho=0.18) and Urea (U)/PCT (rho=0.19) were identified. Simple linear regression showed poor interaction between Cr/U and PCT concentrations (Cr R2=0.03 and U R2=0.018). Similar results were observed during multiple linear regression analysis (Cr R2=0.046 and U R2=0.013). CONCLUSIONS: Although PCT concentrations were slightly higher in patients with AKI, high PCT concentrations are not explained by AKI and could be warning sign of a potential bacterial infection.

Prediction of pathological response to neoadjuvant treatment in rectal cancer with a two-protein immunohistochemical score derived from stromal gene-profiling.

BACKGROUND: Preoperative chemoradiotherapy followed by surgical mesorectal resection is the standard of care for locally advanced rectal carcinomas. Yet, predicting that patients will respond to treatment remains an unmet clinical challenge. EXPERIMENTAL DESIGN: Using laser-capture microdissection we isolated RNA from stroma and tumour glands from prospective pre-treatment samples (n = 15). Transcriptomic profiles were obtained hybridising PrimeView Affymetrix arrays. We modelled a carcinoma-associated fibroblast-specific genes filtering data using GSE39396. RESULTS: The analysis of differentially expressed genes of stroma/tumour glands from responder and non-responder patients shows that most changes were associated with the stromal compartment; codifying mainly for extracellular matrix and ribosomal components. We built a carcinoma-associated fibroblast (CAF) specific classifier with genes showing changes in expression according to the tumour regression grade (FN1, COL3A1, COL1A1, MMP2 and IGFBP5). We assessed these five genes at the protein level by means of immunohistochemical staining in a patient's cohort (n = 38). For predictive purposes we used a leave-one-out cross-validated model with a positive predictive value (PPV) of 83.3%. Random Forest identified FN1 and COL3A1 as the best predictors. Rebuilding the leave-one-out cross-validated regression model improved the classification performance with a PPV of 93.3%. An independent cohort was used for classifier validation (n = 36), achieving a PPV of 88.2%. In a multivariate analysis, the two-protein classifier proved to be the only independent predictor of response. CONCLUSION: We developed a two-protein immunohistochemical classifier that performs well at predicting the non-response to neoadjuvant treatment in rectal cancer.

Extracolonic Cancer in Inflammatory Bowel Disease: Data from the GETECCU Eneida Registry.

OBJECTIVES: The objective of this study was (a) To know the prevalence and distribution of extracolonic cancer (EC) in patients with inflammatory bowel disease (IBD); (b) To estimate the incidence rate of EC; (c) To evaluate the association between EC and treatment with immunosuppressants and anti-tumor necrosis factor (TNF) agents. METHODS: This was an observational cohort study. INCLUSION CRITERIA: IBD and inclusion in the ENEIDA Project (a prospectively maintained registry) from GETECCU. EXCLUSION CRITERIA: Patients with EC before the diagnosis of IBD, lack of relevant data for this study, and previous treatment with immunosuppressants other than corticosteroids, thiopurines, methotrexate, or anti-TNF agents. The Kaplan-Meier method was used to evaluate the impact of several variables on the risk of EC, and any differences between survival curves were evaluated using the log-rank test. Stepwise multivariate Cox regression analysis was used to investigate factors potentially associated with the development of EC, including drugs for the treatment of IBD, during follow-up. RESULTS: A total of 11,011 patients met the inclusion criteria and were followed for a median of 98 months. Forty-eight percent of patients (5,303) had been exposed to immunosuppressants or anti-TNF drugs, 45.8% had been exposed to thiopurines, 4.7% to methotrexate, and 21.6% to anti-TNF drugs. The prevalence of EC was 3.6%. In the multivariate analysis, age (HR=1.05, 95% CI=1.04-1.06) and having smoked (hazards ratio (HR)=1.47, 95% confidence interval (CI)=1.10-1.80) were the only variables associated with a higher risk of EC. CONCLUSIONS: Neither immunosuppressants nor anti-TNF drugs seem to increase the risk of EC. Older age and smoking were associated with a higher prevalence of EC.

Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study.

OBJECTIVES: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed. METHODS: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included. RESULTS: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe. CONCLUSIONS: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

Boceprevir plus pegylated interferon/ribavirin to re-treat hepatitis C virus genotype 1 in HIV-HCV co-infected patients: final results of the Spanish BOC HIV-HCV Study.

INTRODUCTION: Boceprevir (BOC) was one of the first oral inhibitors of hepatitis C virus (HCV) NS3 protease to be developed. This study assessed the safety and efficacy of BOC+pegylated interferon-α2a/ribavirin (PEG-IFN/RBV) in the retreatment of HIV-HCV co-infected patients with HCV genotype 1. METHODS: This was a phase III prospective trial. HIV-HCV (genotype 1) co-infected patients from 16 hospitals in Spain were included. These patients received 4 weeks of PEG-IFN/RBV (lead-in), followed by response-guided therapy with PEG-IFN/RBV plus BOC (a fixed 44 weeks was indicated in the case of cirrhosis). The primary endpoint was the sustained virological response (SVR) rate at 24 weeks post-treatment. Efficacy and safety were evaluated in all patients who received at least one dose of the study drug. RESULTS: From June 2013 to April 2014, 102 patients were enrolled, 98 of whom received at least one treatment dose. Seventy-three percent were male, 34% were cirrhotic, 23% had IL28b CC, 65% had genotype 1a, and 41% were previous null responders. The overall SVR rate was 67%. Previous null-responders and cirrhotic patients had lower SVR rates (57% and 51%, respectively). Seventy-six patients (78%) completed the therapy scheme; the most common reasons for discontinuation were lack of response at week 12 (12 patients) and adverse events (six patients). CONCLUSIONS: Response-guided therapy with BOC in combination with PEG-IFN/RBV led to an overall SVR rate of 67%, but an SVR rate of only 51% in patients with cirrhosis. The therapy was generally well tolerated. Although the current standards of care do not include BOC+PEG-IFN/RBV, the authors believe that this combination can be beneficial in situations where new HCV direct antiviral agent interferon-free therapies are not available yet.

Chronic diarrhoea: Definition, classification and diagnosis / Diarrea crónica: definición, clasificación y diagnóstico

Chronic diarrhoea is a common presenting symptom in both primary care medicine and in specialized gastroenterology clinics. It is estimated that >5% of the population has chronic diarrhoea and nearly 40% of these patients are older than 60 years. Clinicians often need to select the best diagnostic approach to these patients and choose between the multiple diagnostic tests available. In 2014 the Catalan Society of Gastroenterology formed a working group with the main objective of creating diagnostic algorithms based on clinical practice and to evaluate diagnostic tests and the scientific evidence available for their use. The GRADE system was used to classify scientific evidence and strength of recommendations. The consensus document contains 28 recommendations and 6 diagnostic algorithms. The document also describes criteria for referral from primary to specialized care.

La diarrea crónica es un síntoma de presentación frecuente, tanto en las consultas de medicina de familia como en las de digestivo. Se estima que >5% de la población sufre diarrea crónica y que cerca del 40% de estos sujetos son mayores de 60 años. El clínico se enfrenta con frecuencia a la necesidad de decidir cuál es el mejor enfoque diagnóstico de estos pacientes y elegir entre las múltiples pruebas diagnósticas existentes. En 2014 la Societat Catalana de Digestologia creó un grupo de trabajo con el objetivo principal de crear algoritmos diagnósticos en base a la práctica clínica y evaluar las pruebas diagnósticas disponibles y la evidencia científica para su utilización. Para clasificar la evidencia científica y la fuerza de las recomendaciones se utilizó el sistema GRADE. Se han establecido 28 recomendaciones y 6 algoritmos diagnósticos. Se describen los criterios de derivación desde medicina primaria a digestivo de un paciente con diarrea crónica.

Unclassifiable arrhythmic cardiomyopathy associated with Emery-Dreifuss caused by a mutation in FHL1.

Emery-Dreifuss muscular dystrophy (EDMD) is a heterogeneous genetic disorder characterized by peripheral muscular weakness often associated with dilated cardiomyopathy. We characterize clinically a large family with a mutation in FHL1 gene (p.Cys255Ser). Penetrance was 44%, 100% for males and 18% for females. The heart was the main organ involved. Affected adult males had mild hypertrophy, systolic dysfunction and restriction with non-dilated ventricles. Carriers had significant QTc prolongation. The proband presented with resuscitated cardiac arrest. There were two transplants. Pathological study of explanted heart showed fibrofatty replacement and scarring consistent with arrhythmogenic cardiomyopathy and prominent left ventricular trabeculations. Myopathic involvement was evident in all males. Females had no significant neuromuscular disease. Mutations in FHL1 cause unclassifiable cardiomyopathy with coexisting EDMD. Prognosis is poor and systolic impairment and arrhythmias are frequent. Thrombopenia and raised creatine phosphokinase should raise suspicion of an FHL-1 disorder in X-linked cardiomyopathy.

Outcome of neuropsychiatric symptoms related to an antiretroviral drug following its substitution by nevirapine: the RELAX study.

OBJECTIVES: The primary objective was to evaluate the improvement in neuropsychiatric symptoms attributed to an antiretroviral drug after that drug was substituted with nevirapine. The secondary objective was to evaluate the impact on patient adherence and quality of life. METHODS: A prospective, observational study was carried out that included patients with HIV-1 plasma suppression for whom an antiretroviral drug was substituted with nevirapine because of central nervous system (CNS) side effects, a Pittsburgh Sleep Quality Index (PSQI) score > 5 or a Hospital Anxiety and Depression Scale (HADS) score ≥ 10, and who had not initiated psychoactive drug treatment during the prior 6 weeks. Evaluations were carried out at baseline and 1 and 3 months after the switch using the PSQI, HADS, Epworth Sleepiness Scale, Medical Outcomes Study-Short Form 30 items (MOS-SF-30) and Simplified Medication Adherence Questionnaire (SMAQ). RESULTS: A total of 129 patients were included in the study. The drug substituted was mainly efavirenz (89.9%), and reasons for the switch included sleep disturbances (75.2%), anxiety (65.1%), depression (38.7%), attention disturbances (31%), and other reasons (31%), with a mean of 2.4 neuropsychiatric disturbances per patient. A statistically significant improvement was observed in all the tests evaluating neuropsychiatric symptoms and adherence at 1 and 3 months. The CD4 lymphocyte count remained stable (P = 0.096). Three (2.3%) patients had a detectable plasma HIV-1 RNA at the end of the study. Nine patients (6.9%) withdrew because of nevirapine-related toxicity (rash in seven patients and hypertransaminasaemia in two patients, none of which were > grade 2). CONCLUSIONS: The switch to nevirapine from a drug causing neuropsychiatric disturbances (primarily efavirenz) in subjects with virological suppression was effective in resolving those disturbances, with an improvement in all the parameters studied. This led to better adherence to treatment and quality of life, with no detrimental effect on their immunological and virological control.

Randomised clinical trial: colestyramine vs. hydroxypropyl cellulose in patients with functional chronic watery diarrhoea.

BACKGROUND: Idiopathic bile acid malabsorption (BAM) has been suggested as a cause of chronic watery diarrhoea, with a response to colestyramine in 70% of patients. However, the efficacy of this drug has never been investigated in placebo-controlled trials. AIM: To evaluate the efficacy of colestyramine as compared with hydroxypropyl cellulose in the treatment of functional chronic watery diarrhoea. METHODS: Patients with chronic watery diarrhoea were randomly assigned to groups given colestyramine sachets 4 g twice daily (n = 13) or identical hydroxypropyl cellulose sachets (n = 13) for 8 weeks. The primary end-point was clinical remission defined as a mean of 3 or fewer stools per day during the week before the visit, with less than 1 watery stool per day. A secondary end-point was the reduction in daily watery stool number. SeHCAT test was performed in all patients, but an abnormal test was not a prerequisite to be included. RESULTS: All included patients had a SeHCAT 7-day retention ≤20%. There were no statistical differences in the percentage of patients in clinical remission at week 8 between colestyramine and hydroxypropyl cellulose with either intention-to-treat (53.8% vs. 38.4%; P = 0.43) or per-protocol (63.6% vs. 38.4%; P = 0.22) analyses. However, the mean per cent decrease in watery stool number was significantly higher with colestyramine than with hydroxypropyl cellulose (-92.4 ± 3.5% vs. -75.8 ± 7.1%; P = 0.048). The rate of adverse events related to study drugs did not differ between groups. CONCLUSIONS: Colestyramine (4 g twice daily) is effective and safe for short-term treatment of patients with chronic watery diarrhoea presumably secondary to BAM. Clinical Trials Register number EudraCT 2009-011149-14.

Identification of Environmental Chemicals Associated with the Development of Toxicant-associated Fatty Liver Disease in Rodents.

BACKGROUND: Toxicant-associated fatty liver disease (TAFLD) is a recently identified form of nonalcoholic fatty liver disease (NAFLD) associated with exposure to industrial chemicals and environmental pollutants. Numerous studies have been conducted to test the association between industrial chemicals/environmental pollutants and fatty liver disease both in vivo and in vitro. OBJECTIVES: The objective of the article is to report a list of chemicals associated with TAFLD. METHODS: Two federal databases of rodent toxicology studies-Toxicological Reference Database (ToxRefDB; Environmental Protection Agency) and Chemical Effects in Biological Systems (CEBS, National Toxicology Program)-were searched for liver end points. Combined, these 2 databases archive nearly 2,000 rodent studies. Toxicant-associated steatohepatitis (TASH) descriptors including fatty change, fatty necrosis, Oil red O-positive staining, steatosis, and lipid deposition were queried. RESULTS: Using these search terms, 123 chemicals associated with fatty liver were identified. Pesticides and solvents were the most frequently identified chemicals, while polychlorinated biphenyls (PCBs)/dioxins were the most potent. About 44% of identified compounds were pesticides or their intermediates, and >10% of pesticide registration studies in ToxRefDB were associated with fatty liver. Fungicides and herbicides were more frequently associated with fatty liver than insecticides. CONCLUSION: More research on pesticides, solvents, metals, and PCBs/dioxins in NAFLD/TAFLD is warranted due to their association with liver damage.