Treatment patterns and intensification within 5 year of follow-up of the first-line anti-TNFα used for the treatment of IBD: Results from the VERNE study.

BACKGROUND: Anti-TNFα represent one of the main treatment approaches for the management of inflammatory bowel diseases (IBD). Therefore,the evaluation of their treatment patterns over time provides valuable insights about the clinical value of therapies and associated costs. AIMS: To assess the treatment patterns with the first anti-TNFα in IBD. METHODS: Retrospective, observational study. RESULTS: 310 IBD patients were analyzed along a 5-year follow-up period. 56.2% of Crohn's disease (CD) patients started with adalimumab (ADA), while 43.8% started with infliximab (IFX). 12.9% of ulcerative colitis (UC) patients initiated with ADA, while 87.1% initiated with IFX. Treatment intensification was required in 28.9% of CD and 37.1% of UC patients. Median time to treatment intensification was shorter in UC than in CD (5.3 vs. 14.3 months; p = 0.028). Treatment discontinuation due to reasons other than remission were observed in 40.7% of CD and 40.5% of UC patients, although, in UC patients there was a trend to lower discontinuation rates with IFX (36.6%) than with ADA (66.7%). Loss of response accounted for approximately one-third of discontinuations, in both CD and UC. CONCLUSIONS: Around one-third of IBD biologic-naive patients treated with an anti-TNFα required treatment intensification (earlier in UC) and around 40% discontinued the anti-TNFα due to inappropriate disease control.

Post-operative morbidity and mortality of a cohort of steroid refractory acute severe ulcerative colitis: Nationwide multicenter study of the GETECCU ENEIDA Registry.

BACKGROUND: Despite the increased use of rescue medical therapies for steroid refractory acute severe ulcerative colitis, mortality related to this entity still remains high. We aimed to assess the mortality and morbidity related to colectomy and their predictive factors in steroid refractory acute severe ulcerative colitis, and to evaluate the changes in mortality rates, complications, indications of colectomy, and the use of rescue therapy over time. METHODS: We performed a multicenter observational study of patients with steroid refractory acute severe ulcerative colitis requiring colectomy, admitted to 23 Spanish hospitals included in the ENEIDA registry (GETECCU) from 1989 to 2014. Independent predictive factors of mortality were assessed by binary logistic regression analysis. Mortality along the study was calculated using the age-standardized rate. RESULTS: During the study period, 429 patients underwent colectomy, presenting an overall mortality rate of 6.3% (range, 0-30%). The main causes of death were infections and post-operative complications. Independent predictive factors of mortality were: age ≥50 years (OR 23.34; 95% CI: 6.46-84.311; p < 0.0001), undergoing surgery in a secondary care hospital (OR 3.07; 95% CI: 1.01-9.35; p = 0.047), and in an emergency setting (OR 10.47; 95% CI: 1.26-86.55; p = 0.029). Neither the use of rescue medical treatment nor the type of surgical technique used (laparoscopy vs. open laparotomy) influenced mortality. The proportion of patients undergoing surgery in an emergency setting decreased over time (p < 0.0001), whereas the use of rescue medical therapy prior to colectomy progressively increased (p > 0.001). CONCLUSIONS: The mortality rate related to colectomy in steroid refractory acute severe ulcerative colitis varies greatly among hospitals, reinforcing the need for a continuous audit to achieve quality standards. The increasing use of rescue therapy is not associated with a worse outcome and may contribute to reducing emergency surgical interventions and improve outcomes.

Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease: Results from the Multicenter European TEDDY Study.

OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. RESULTS: The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNFα agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5-4.3)). CONCLUSIONS: In utero exposure to anti-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.

Long-Term Efficacy and Safety of Cyclosporine in a Cohort of Steroid-Refractory Acute Severe Ulcerative Colitis Patients from the ENEIDA Registry (1989-2013): A Nationwide Multicenter Study.

OBJECTIVES: To determine the efficacy and safety of cyclosporine (CyA) in a large national registry-based population of patients with steroid-refractory (SR) acute severe ulcerative colitis (ASUC) and to establish predictors of efficacy and adverse events. METHODS: Multicenter study of SR-ASUC treated with CyA, based on data from the ENEIDA registry. SR-ASUC patients treated with infliximab (IFX) or sequential rescue therapy (CyA-IFX or IFX-CyA) were used as comparators. RESULTS: Of 740 SR-ASUC patients, 377 received CyA, 131 IFX and 63 sequential rescue therapy. The cumulative colectomy rate was higher in the CyA (24.1%) and sequential therapy (32.7%) than in the IFX group (14.5%; P=0.01) at 3 months and 5 years. There were no differences in early and late colectomy between CyA and IFX in patients treated after 2005. 62% of patients receiving CyA remained colectomy-free in the long term (median 71 months). There were no differences in mortality between CyA (2.4%), IFX (1.5%) and sequential therapy (0%; P=0.771). The proportion of patients with serious adverse events (SAEs) was lower in CyA (15.4%) than in IFX treated patients (26.5%) or sequential therapy (33.4%; P<0.001). This difference in favor of CyA was maintained when only patients treated after 2005 were analyzed. CONCLUSIONS: Treatment with CyA showed a lower rate of SAE and a similar efficacy to that of IFX thereby supporting the use of either CyA or IFX in SR-ASUC. In addition, the risk-benefit of sequential CyA-IFX for CyA non-responders is acceptable.

Population mobility and the changing epidemics of HIV-2 in Portugal.

INTRODUCTION: Portugal is the European country with the highest frequency of HIV-2 infection, which is mainly concentrated in West Africa. The cumulative number of notified HIV-2 infections in Portugal was 1813 by the end of December 2008. To better characterize the dynamics of HIV-2 infection in the country and to obtain data that may be of use in the prevention of the spread of HIV-2, we evaluated a large pooled sample of patients. PATIENTS AND METHODS: Five Portuguese hospitals provided data on HIV-2-infected patients from 1984 to the end of 2007. Data concerning demographic characteristics and clinical variables were extracted. Patients were stratified according to date of diagnosis in approximately 5-year categories. RESULTS: The sample included 442 patients, accounting for 37% of all HIV-2 infections notified in Portugal during that period. HIV-2-infected patients showed clearly different characteristics according to the period of diagnosis. Until 2000, the majority of HIV-2-infected patients were Portuguese-born males living in the north of the country. From 2000 to 2007, most of the patients diagnosed with HIV-2 infection had a West African origin, were predominantly female and were living in the capital, Lisbon. The average age at diagnosis and loss to follow-up significantly increased over time. CONCLUSION: HIV-2 infection has been documented in Portugal since the early 1980s and its epidemiology appears to reflect changes in population movement. These include the movements of soldiers and repatriates from African territories during the independence wars and, later, migration and mobility from high-endemicity areas. The findings of this study stress the importance of promoting migrant-sensitive health care.

Evaluación del efecto de diferentes cepas de levadura (Montrachet, K1-V1116, EC-1118, 71B-1122 y IVC-GRE ®) y clarificantes sobre los atributos sensoriales del vino de naranja criolla (Citrus sinensis) / Evaluation of effect of various strains of yeast (Montrachet, K1-V1116, EC-1118, 71B-1122 y IVC-GRE ®) and clearer on the sensory attributes orange wine (Citrus sinensis)

En este trabajo se evaluó el efecto de diferentes cepas de levadura (Montrachet, K1-V1116, EC-1118, 71B-1122 y IVC-GRE ®) sobre los atributos sensoriales del vino de naranja. Estos atributos fueron medidos utilizando la escala modificada de UC Davis. En una prueba de ordenamiento para determinar el mejor tratamiento de clarificación se determinó que la gelatina por sí sola no causa efecto sobre el atributo apariencia general, la combinación de la gelatina y la microfiltración tienen un efecto positivo sobre la apariencia del vino de naranja. Los cinco vinos tratados con diferentes levaduras presentaron diferencias significativas sobre la puntuación total, acidez total, sabor y calidad en general. En términos del efecto de las levaduras, la evaluación sensorial realizada a los vinos mostró que el de naranja con la levadura K1-V1116 fue el que sobresalió en términos de puntuación en los promedios de casi todos los atributos analizados por el panel sensorial.

In this Wort was evaluated the effect of different types of strains of yeast (Montrachet, K1-V1116, EC-1118, 71B-1122 y IVC-GRE) over the sensorial attributes of orange wines were also studied. These attributes were measured in a modified scale of UC Davis. By using an order test in order to know the best cleared treatment, it was determined that gelatin by itself does not cause any effect over the general quality attribute, but the combination of gelatin and microfiltration, cause a positive effect over the orange wine appearance. The five wines treated with different yeasts presented significant differences on individual scores, total acidy, flavor and general quality of the UC Davis scale. The sensorial evaluation of wines showed that the yeast K1-V1116 produced the best rated orange wine. This wine was significantly different over many attributes when compared with the other wines evaluated by the sensorial panel.

Molecular subtyping of Treponema pallidum subsp. pallidum in Lisbon, Portugal.

The objectives of this study were to evaluate the reproducibility of a molecular method for the subtyping of Treponema pallidum subsp. pallidum and to discriminate strains of this microorganism from strains from patients with syphilis. We studied 212 specimens from a total of 82 patients with different stages of syphilis (14 primary, 7 secondary and 61 latent syphilis). The specimens were distributed as follows: genital ulcers (n = 9), skin and mucosal lesions (n = 7), blood (n = 82), plasma (n = 82), and ear lobe scrapings (n = 32). The samples were assayed by a PCR technique to amplify a segment of the polymerase gene I (polA). Positive samples were typed on the basis of the analysis of two variable genes, tpr and arp. Sixty-two of the 90 samples positive for polA yielded typeable Treponema pallidum DNA. All skin lesions in which T. pallidum was identified (six of six [100%]) were found to contain enough DNA for typing of the organism. It was also possible to type DNA from 7/9 (77.7%) genital ulcer samples, 13/22 (59.1%) blood samples, 20/32 (62.5%) plasma samples, and 16/21 (76.2%) ear lobe scrapings. The same subtype was identified in all samples from the same patient. Five molecular subtypes (subtypes 10a, 14a, 14c, 14f, and 14g) were identified, with the most frequently found subtype being subtype 14a and the least frequently found subtype being subtype 10a. In conclusion, the subtyping technique used in this study seems to have good reproducibility. To our knowledge, subtype 10a was identified for the first time. Further studies are needed to explain the presence of this subtype in Portugal, namely, its relationship to the Treponema pallidum strains circulating in the African countries where Portuguese is spoken.

Detection of Treponema pallidum sp pallidum DNA in latent syphilis.

In this study, polymerase chain reaction (PCR) techniques were used to detect Treponema pallidum DNA in samples from patients with latent syphilis. Sixty-nine patients with latent syphilis and 18 with treated syphilis were included. Whole blood, plasma, sera and ear scrapings, totalling 235 samples from patients with latent syphilis, were obtained. Three PCR assays (47-PCR, polA-PCR and M-PCR assays) were performed. The 47-PCR yielded the highest number of positive samples -92/235 (39.1%), followed by M-PCR -90/235 (38.3%) and polA-PCR -73/235 (31.1%). Ear scrapings presented the highest number of positives (47/84 -56%), followed by plasma samples (36/84 -42.9%), whole blood (32/84 -38.1%) and sera (21/84 -25%). In conclusion, we have confirmed that T. pallidum can be found in blood of patients with latent syphilis. The 47-PCR technique was found to be the most sensitive, whereas ear lobe scrapings seem to be the best specimen for detection of T. pallidum DNA in latent syphilis.

Actualización del trasplante hepático en la hepatitis C crónica / No disponible

No disponible

Incidence, risk factors and clinical course of thiopurine-induced liver injury in patients with inflammatory bowel disease.

BACKGROUND: The incidence of thiopurine-induced hepatotoxicity in patients with inflammatory bowel disease varies in different studies. AIMS: To assess the rate of thiopurine-induced liver toxicity in patients with inflammatory bowel disease; to determine the predictive factors and to characterize its clinical course and management. METHODS: A cohort of 161 patients was prospectively followed for a median of 271 days. Hepatotoxicity was established when alanine transaminase or alkaline phosphatase plasma levels were greater than twice the upper normal limit. RESULTS: Abnormal liver function was detected in 21 patients (13%; 95% CI: 7-18). Hepatotoxicity occurred in 16 patients (10%; 95% CI: 6-16) after a median of 85 days. In five cases, treatment was withdrawn due to hepatotoxicity. Use of corticosteroids was associated with hepatotoxicity (OR: 4.94; 95% CI: 1.01-23.98) with antitumour necrosis factor concomitant therapy showing a protective role (OR: 0.3; 95% CI: 0.1-3.1). gamma-Glutamyl transferase plasma levels at the onset of hepatotoxicity showed the best predictive value for treatment withdrawal (area under the receiver operating characteristic curve: 0.95). CONCLUSIONS: The incidence of hepatotoxicity in inflammatory bowel disease patients receiving thiopurines is relevant, mainly in patients co-treated with corticosteroids. gamma-Glutamyl transferase plasma level is a useful biomarker in therapy withdrawal prediction.

Evaluación de la calidad de las prescripciones a los pacientes ingresados / Prescription quality evaluation in hospital patients

No disponible

Prevención de la gastropatía por antiinflamatorios no esteroides: seguimiento de la adherencia al protocolo / Prevention of non-steroidal antiinflammatory drugs-induced gastropathy: follow up of protocol adherence

Objetivo: consensuar y evaluar el cumplimiento del protocolo para la profilaxis de la gastropatía inducida por antiinflamatorios no esteroides, con omeprazol 20 mg al día.Pacientes y método: se han realizado 3 estudios transversales de los pacientes ingresados en nuestro hospital antes de la implantación del protocolo, inmediatamente después y al cabo de 6 meses.Resultados: entre el 16 y 24 por ciento de los pacientes ingresados en nuestro hospital toman fármacos antiinflamatorios no esteroides.Antes de la aplicación del protocolo un 34,7 por ciento de la prescripciones coincidían con él. Tras su implantación la adherencia de los médicos prescriptores al protocolo mejoró hasta el 51,8 por ciento ( 2 =5,27 p=0,02) y a los 6 meses se alcanzó un 51,4 por ciento de adherencia, mejoría que continuó siendo significativa respecto a la fase previa ( 2 =5,74 p=0,01). El principal motivo de incumplimiento fue la utilización de ranitidina en lugar de omeprazol. Uno de los métodos más útiles para mejorar la adhesión ha sido la reunión con los servicios médicos que más emplean los antiinflamatorios, centrada específicamente en la utilización del protocolo.Conclusiones: el seguimiento del protocolo muestra una mejoría del cumplimiento tras la fase de implantación que se mantiene al cabo de 6 meses. La adherencia de los médicos prescriptores al tratamiento, sin embargo, es inferior a la esperada. (AU)

Efecto de la incontinencia urinaria y la dependencia para la alimentación en la institucionalización de pacientes geriátricos agudos / Effect of urinary incontinence and dependence for feeding on the institutionalization of acute geriatric patients

OBJETIVO: Valorar el efecto de la presencia de incontinencia urinaria (IU) y dependencia para la alimentación (DA) en la institucionalización de pacientes ancianos atendidos por una unidad de valoración geriátrica en un hospital de agudos. MATERIAL Y MÉTODOS: Estudio prospectivo observacional donde se analiza en 302 pacientes geriátricos consecutivos ingresados por patología aguda médica y quirúrgica, la presencia de IU y DA, así como la patología al ingreso, la comorbilidad existente, el estado cognitivo, la funcionalidad, el soporte social y el destino hacia instituciones geriátricas al alta hospitalaria. RESULTADOS: El 51,9 per cent de los pacientes presentaban IU y el 39,7 per cent DA. En general los pacientes con IU y DA, mostraron peores puntuaciones en los tests de Barthel y Pfeiffer, 33,8 (DE 18,4) vs 60,1 (DE 17,0) y 2,91 (DE 3,5) vs 0,27 (DE 1,0) (p< 0,0001) respectivamente, a la vez que un mayor índice de comorbilidad de Charlson, 1,95 (DE 1,7) vs 1,23 (DE 1,59) (p< 0,01). La institucionalización se observó en 46 pacientes (15,23 per cent) con IU y DA vs 5 pacientes (1,56 per cent) sin IU ni DA (p< 0,0001). CONCLUSIONES: La IU y la DA son frecuentes en nuestro medio hospitalario y aisladas o asociadas se constituyen como factores de riesgo para la institucionalización de pacientes geriátricos atendidos por patología aguda (AU)

Prevention of non-steroidal antiinflammatory drugs-induced gastropathy: follow up of protocol adherence.

OBJECTIVE: To reach a consensus on and evaluate the compliance of the protocol for the prophylaxis of gastropathy induced by non-steroidal anti-inflammatory drugs with 20 mg omeprazole per day. PATIENTS AND METHOD: Three transversal studies have been carried out on patients admitted to our hospital before establishing the protocol, immediately after and 6 months later. RESULTS: Between 16 and 24% of patients admitted to our hospital take non-steroidal anti-inflammatory drugs. Before the application of the protocol 34.7% of prescriptions coincided with this use. After its establishment adherence by the prescribing doctors improved to 51.8% (c2 = 5.27, p = 0.02) and at 6 months it reached 51.4% adherence, an improvement that continued being significative (c2 = 5.74, p = 0.01). The main reason for non-compliance was the use of ranitidine instead of omeprazole. One of the most useful methods for improving adhesion has been meeting with the medical services that most use the anti-inflammatory drugs, focussing specifically on the use of the protocol. CONCLUSIONS: The follow-up of the protocol shows an improvement in compliance after the establishment stage which is maintained after 6 months. Adherence by the prescribing doctors to the treatment, nevertheless, is lower than had been hoped.

Neisseria meningitidis native valve endocarditis. A case report.

The so-called nonpathogenic neisseriae are common inhabitants of the upper respiratory tract in humans and are not usually regarded as pathogens. Neisseria meningitidis on the contrary may cause severe disease. These organisms are an uncommon cause of infective endocarditis. The authors report a case of a 64 year-old male, type II diabetic, previously asymptomatic, admitted to hospital because of fever, aphasia and right hemi-paresis. A systolic murmur was heard at the cardiac apex, and three blood cultures were positive for Neisseria meningitidis. The echocardiogram showed a vegetation on the posterior leaflet of the mitral valve, allowing the diagnosis of meningococcal endocarditis. The patient's clinical condition improved on intravenous penicillin therapy, and regression of fever, disappearance of the neurological signs and of the mitral valve vegetation were observed.