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INTRODUCTION: Accelerated dose infliximab (IFX) induction is associated with reduced short-term colectomy rate in acute severe ulcerative colitis (ASUC). Data on medium/long-term outcomes of this strategy are limited. AIMS: Evaluate medium/long-term outcomes in patients receiving IFX induction for ASUC, comparing accelerated dose (AD) and standard dose (SD) induction. METHODS: Retrospective study of consecutive patients admitted with corticosteroid-refractory ASUC in four tertiary referral centres within INITIative IBD research network (www.initiativeibd.ie). IFX rescue was given either as SD (weeks 0, 2, 6) or AD (<28 days) from January 2010 to September 2017. AD induction has been utilised in participating centres since 2014. Consequently SD patients were subdivided based on time period of IFX rescue: historical SD group (SD1) (2010-2013) and current SD group (SD2) (2014-2017). Primary endpoint was time to colectomy; secondary endpoint was time to IFX discontinuation if induction was complete. RESULTS: 145 patients received rescue IFX (AD=58, SD1=32, SD2=55). Disease severity at induction was comparable between AD and SD1 groups; however, SD2 group had less severe disease: median C-reactive protein (CRP) 39, 44 and 20 mg/L for AD, SD1 and SD2 groups, respectively (p=0.026, Kruskal-Wallis); median CRP: albumin ratio was 1.4, 1.8 and 0.6 (p=0.016). Median follow-up for AD, SD1 and SD2 groups was 1.6 (IQR 1.1-3.1), 4.9 (IQR 2.6-5.5) and 1.5 (IQR 0.9-2.3) years. Time to colectomy was shorter in SD1 (log rank p=0.0013); no significant difference in time to colectomy was observed comparing AD and SD2 groups (log rank p=0.32). 123 patients (84%) completed IFX induction and received maintenance therapy. Time to IFX discontinuation was shorter in SD1 (log rank p=0.009). CONCLUSION: Time to colectomy is significantly prolonged with use of AD IFX in selected ASUC patients with more severe disease. Historical use of standard IFX induction for all ASUC patients is associated with inferior long-term outcomes.
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BACKGROUND & AIMS: Patients with Crohn's disease or ulcerative colitis have relatively high levels of stress and psychological dysfunction. Acceptance and commitment therapy (ACT) is a psychological intervention that comprises acceptance and mindfulness procedures, along with commitment and behavior change strategies, to increase psychological flexibility and reduce stress. We performed a randomized controlled trial to investigate the effect of ACT on stress in patients with inflammatory bowel diseases (IBD). METHODS: A total of 122 patients with quiescent or stable, mildly active IBD were randomly assigned to an 8-week ACT program or treatment as usual (control group). Clinical, demographic, disease activity, and psychological data and blood and feces were collected at baseline and at 8 weeks and 3 months after the intervention (week 20). Scalp hair was collected at baseline and week 20 for measurement of steroid concentrations. The primary endpoint was change in stress symptoms, assessed with the Depression Anxiety Stress Scale. Secondary endpoints included changes in perceived stress, anxiety, depression, quality-of-life domains, disease activity, and cortisol concentration in hair. RESULTS: Overall, 79 participants were included in the complete case intention-to-treat analysis. There were 39% and 45% reductions in stress in the treatment group from baseline to 8 and 20 weeks, respectively, compared with 8% and 11% in the control group (group × time interaction, P = .001). ACT was associated with reduced perceived stress (P = .036) and depression (P = .010), but not anxiety (P = .388), compared with control individuals. In the intention-to-treat analysis, changes in all 4 quality-of-life domains over time were similar in the ACT and control groups. In the per-protocol analysis, the overall well-being quality-of-life domain improved in the ACT group compared with the control group (P = .009). Subjective and objective disease activity measurements were similar between groups over the study period (all P values >.05). Hair cortisol concentrations correlated with stress (rs = 0.205, P = .050) and anxiety (rs = 0.208, P = .046) at baseline but did not change significantly in the ACT group over the study period compared with the control group (P = .831). CONCLUSION: In a randomized controlled trial of patients with IBD, an 8-week ACT therapy course improved stress and other indices of psychological health.ClinicalTrials.gov Identifier: NCT02350920.
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Terapia de Aceptación y Compromiso , Ansiedad/terapia , Colitis Ulcerosa/psicología , Enfermedad de Crohn/psicología , Depresión/terapia , Estrés Psicológico/terapia , Adulto , Ansiedad/etiología , Depresión/etiología , Femenino , Cabello/química , Humanos , Hidrocortisona/análisis , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Percepción , Progesterona/análisis , Escalas de Valoración Psiquiátrica , Calidad de Vida , Índice de Severidad de la Enfermedad , Estrés Psicológico/sangre , Estrés Psicológico/etiología , Testosterona/análisisRESUMEN
BACKGROUND: Consensus guidelines from the European Crohns and Colitis Organisation conclude that optimizing quality of care in inflammatory bowel disease [IBD] involves information and education. However, there is no standardized patient education programme in IBD and education varies from centre to centre. AIM: To assess patients' education needs in IBD to facilitate design of a patient education programme. METHODS: We created focus groups of 12 patients with IBD and used qualitative analysis to generate hypotheses. We then developed a quantitative questionnaire which was disseminated to 327 IBD patients attending three different centres. Five patients declined to participate and thus 322 patients (159 [49%] male, 180 [58%] Crohn's disease, median age 38 years and disease duration 7 years) were included. RESULTS: Patients were most keen to receive education on medications, 'what to expect in future', living with IBD and diet. They wanted to receive this information from specialist doctors or nurses and believed it could improve their quality of life. Though the internet was the preferred source of general information [i.e. planning holidays], it was the least preferred source of IBD education. While there was a trend for females to prefer peer education, family history of IBD was the only statistically significant factor associated with information preferences. CONCLUSION: This is a patient-centred, mixed methodology study on patient education in IBD. Patients' preferences for education include components such as what to expect and diet and patients seem to distrust the internet as an IBD information source. International validation would be valuable to create a consensus education programme.
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Colitis Ulcerosa , Enfermedad de Crohn , Conducta en la Búsqueda de Información , Educación del Paciente como Asunto , Adulto , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Dieta , Femenino , Grupos Focales , Fármacos Gastrointestinales/uso terapéutico , Humanos , Internet , Masculino , Persona de Mediana Edad , Evaluación de Necesidades , Prioridad del Paciente , Calidad de Vida , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Identifying hospitalized patients with acute severe ulcerative colitis (ASUC) who will be refractory to corticosteroid therapy and require rescue therapy remains difficult. Hypoalbuminemia worsens with time during hospitalization and is associated with rapid clearance of and reduced response to infliximab (IFX) rescue. Early use of rescue therapy may therefore be more effective. Simple clinical and laboratory predictors of corticosteroid responsiveness would facilitate earlier use of rescue therapy. MATERIALS AND METHODS: Retrospective study of a prospectively maintained database of 3600 patients attending a single center was conducted. Patients with histologically confirmed ulcerative colitis admitted with ASUC over a 5-year period from January 2010 to December 2014 were identified. All patients initially received intravenous corticosteroids. Patient demographics were collected; C-reactive protein (CRP) and albumin levels were recorded at baseline and during admission. Receiver operating characteristic statistics were used to determine the optimal stool frequency, CRP, albumin, and CRP/albumin ratio (CAR) to predict steroid response. RESULTS: A total of 124 ASUC patients were admitted during a 5-year period. Median follow-up was 2.3 years. A total of 62 patients (50%) were steroid responsive, 55 patients (44%) received rescue IFX, 22 patients (18%) required colectomy within 30 days of admission, whereas a further 14 (11%) required colectomy during follow-up. By receiver operating characteristic statistics, day 3 CAR was a more accurate marker of steroid responsiveness than day 3 CRP or day 3 albumin alone [area under curve=0.75 (P<0.001)]. The optimal CAR to predict response to steroids on day 3 was 0.85 (sensitivity 70%, specificity 76%). When combined with D3 stool frequency, specificity improved to 83%. If at day 3, CAR was >0.85 and stool frequency was >3, the relative risk of steroid nonresponse was significantly raised at 3.9 (95% confidence interval, 2.1-7.2). CONCLUSIONS: Raised D3 CAR is an early predictor of steroid-refractory ASUC. When combined with D3 stool frequency, its predictive ability improves. In patients with predicted steroid nonresponse, early introduction of rescue IFX at this stage may be more effective, before serum albumin falls profoundly.
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Corticoesteroides/uso terapéutico , Antiinflamatorios/uso terapéutico , Proteína C-Reactiva/metabolismo , Colitis Ulcerosa/tratamiento farmacológico , Monitoreo de Drogas/métodos , Fármacos Gastrointestinales/uso terapéutico , Albúmina Sérica Humana/metabolismo , Corticoesteroides/efectos adversos , Adulto , Antiinflamatorios/efectos adversos , Biomarcadores/sangre , Colitis Ulcerosa/sangre , Colitis Ulcerosa/diagnóstico , Bases de Datos Factuales , Femenino , Fármacos Gastrointestinales/efectos adversos , Humanos , Infliximab/uso terapéutico , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Inducción de Remisión , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Insuficiencia del TratamientoRESUMEN
A 35-year old woman with ileocolonic, perianal, and vulval Crohn's disease was treated with subcutaneous ustekinuamb [USK] throughout pregnancy. Dose intervals were shortened from 6-weekly to 4-weekly to maintain clinical remission. The last dose of USK was administered at 33 weeks of gestation, and a healthy baby boy was delivered by caesarean section at 37 weeks. Maternal trough USK levels remained stable during pregnancy. Cord blood USK levels were nearly 2-fold higher than contemporaneous maternal serum levels. To our knowledge, this is the first report of maternal and cord USK levels in a patient with Crohn's disease.
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Enfermedad de Crohn/tratamiento farmacológico , Sangre Fetal/química , Fármacos Gastrointestinales/sangre , Complicaciones del Embarazo/tratamiento farmacológico , Ustekinumab/sangre , Adulto , Femenino , Fármacos Gastrointestinales/análisis , Fármacos Gastrointestinales/uso terapéutico , Humanos , Recién Nacido , Masculino , Embarazo , Ustekinumab/análisis , Ustekinumab/uso terapéuticoRESUMEN
Reflex immunohistochemistry (rIHC) for mismatch repair (MMR) protein expression can be used as a screening tool to detect Lynch Syndrome (LS). Increasingly the mismatch repair-deficient (dMMR) phenotype has therapeutic implications. We investigated the pattern and consequence of testing for dMMR in three Irish Cancer Centres (CCs). CRC databases were analyzed from January 2005-December 2013. CC1 performs IHC upon physician request, CC2 implemented rIHC in November 2008, and CC3 has been performing rIHC since 2004. The number of eligible patients referred to clinical genetic services (CGS), and the number of LS patients per center was determined. 3906 patients were included over a 9-year period. dMMR CRCs were found in 32/153 (21%) of patients at CC1 and 55/536 (10%) at CC2, accounting for 3% and 5% of the CRC population, respectively. At CC3, 182/1737 patients (10%) had dMMR CRCs (P < 0.001). Additional testing for the BRAF V600E mutation, was performed in 49 patients at CC3 prior to CGS referral, of which 29 were positive and considered sporadic CRC. Referrals to CGS were made in 66%, 33%, and 30% of eligible patients at CC1, CC2, and CC3, respectively. LS accounted for CRC in eight patients (0.8%) at CC1, eight patients (0.7%) at CC2, and 20 patients (1.2%) at CC3. Cascade testing of patients with dMMR CRC was not completed in 56%. Universal screening increases the detection of dMMR tumors and LS kindreds. Successful implementation of this approach requires adequate resources for appropriate downstream management of these patients.
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Neoplasias Colorrectales/genética , Reparación de la Incompatibilidad de ADN , Centros Médicos Académicos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Mutación , Fenotipo , Proteínas Proto-Oncogénicas B-raf/genética , Adulto JovenRESUMEN
BACKGROUND AND AIMS: Inflammatory bowel diseases (IBDs) are heterogeneous disorders with complex aetiology. Quantitative genetic studies suggest that only a small proportion of the disease variance observed in IBD is accounted for by genetic variation, indicating a potential role for differential epigenetic regulation in disease aetiology. The aim of this study was to assess genome-wide DNA methylation changes specifically associated with ulcerative colitis (UC), Crohn's disease (CD) and IBD activity. METHODS: DNA methylation was quantified in peripheral blood mononuclear cells (PBMCs) from 149 IBD cases (61 UC, 88 CD) and 39 controls using the Infinium HumanMethylation450 BeadChip. Technical and functional validation was performed using pyrosequencing and the real-time polymerase chain reaction. Cross-tissue replication of the top differentially methylated positions (DMPs) was tested in colonic mucosa tissue samples obtained from paediatric IBD cases and controls. RESULTS: A total of 3196 probes were differentially methylated between CD cases and controls, while 1481 probes were differentially methylated between UC cases and controls. There was considerable (45%) overlap between UC and CD DMPs. The top-ranked IBD-associated PBMC differentially methylated region (promoter region of TRIM39-RPP2) was also significantly hypomethylated in colonic mucosa from paediatric UC patients. In addition, we confirmed TRAF6 hypermethylation using pyrosequencing and found reduced TRAF6 gene expression in PBMCs of IBD patients. CONCLUSIONS: Our data provide new insights into differential epigenetic regulation of genes and molecular pathways, which may contribute to the pathogenesis and activity of IBD.
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Metilación de ADN/genética , Epigénesis Genética/fisiología , Perfilación de la Expresión Génica , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/fisiopatología , Adolescente , Adulto , Factores de Edad , Estudios de Casos y Controles , Niño , Colitis Ulcerosa/genética , Colitis Ulcerosa/fisiopatología , Enfermedad de Crohn/genética , Enfermedad de Crohn/fisiopatología , Progresión de la Enfermedad , Epigénesis Genética/genética , Femenino , Regulación de la Expresión Génica , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Valores de Referencia , Medición de Riesgo , Factores Sexuales , Adulto JovenRESUMEN
BACKGROUND: To evaluate whether changes in expression of CD39 by regulatory T lymphocytes (Treg) impact treatment response in inflammatory bowel disease. To then define the biological role of expression of CD39 on Treg in an animal model of colitis. METHODS: A prospective study of consecutive patients commencing anti-tumor necrosis factor therapy with infliximab (IFX) or adalimumab (ADA), who were then followed for 12 months. Treatment responses were defined both symptomatically and by endoscopy showing mucosal healing. Peripheral blood Tregs were quantified by flow cytometry. Functional importance of CD39 expression by Treg was determined in an adoptive T-cell transfer model of colitis. RESULTS: Forty-seven patients (ulcerative colitis, n = 22; Crohn's disease, n = 25) were recruited; 16 patients were complete responders and 13 nonresponders to anti-tumor necrosis factor. CD39 expression by Treg was lower in active inflammatory bowel disease and increased significantly after treatment in responders (CD39Treg/total Treg; 8% at baseline to 22.5% at late time point, P < 0.001). Responders were more likely to have therapeutic drug levels and in multivariate analysis therapeutic drug levels were associated with higher expression of CD39 by FoxP3 Treg and lower frequencies of interleukin 17A expressing cells. Tregs with genetic deletion of CD39 exhibit decrements in potential to suppress intestinal inflammation in a murine (CD45RB) T-cell transfer model of colitis in vivo, when compared with wild-type Treg. CONCLUSIONS: Increased expression of CD39 by peripheral blood Treg is observed in the setting of clinical and endoscopic remission in inflammatory bowel disease. Deficiency of CD39 expression by Treg can be linked to inability to suppress experimental colitis.
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Anticuerpos Monoclonales/uso terapéutico , Antígenos CD/sangre , Apirasa/sangre , Colitis Ulcerosa/inmunología , Enfermedad de Crohn/inmunología , Factores Inmunológicos/uso terapéutico , Linfocitos T Reguladores/metabolismo , Adalimumab/uso terapéutico , Adulto , Animales , Antiinflamatorios/uso terapéutico , Colitis Ulcerosa/sangre , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/sangre , Enfermedad de Crohn/tratamiento farmacológico , Femenino , Fármacos Gastrointestinales/uso terapéutico , Humanos , Infliximab/uso terapéutico , Interleucina-17/sangre , Masculino , Ratones , Persona de Mediana Edad , Estudios Prospectivos , Inducción de Remisión , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/inmunología , Adulto JovenRESUMEN
BACKGROUND AND AIMS: Psychological stress is associated with inflammatory bowel disease [IBD], but the nature of this relationship is complex. At present, there is no simple tool to screen for stress in IBD clinical practice or assess stress repeatedly in longitudinal studies. Our aim was to design a single-question 'stressometer' to rapidly measure stress and validate this in IBD patients. METHODS: In all, 304 IBD patients completed a single-question 'stressometer'. This was correlated with stress as measured by the Depression Anxiety Stress Scales [DASS-21], quality of life, and disease activity. Test-retest reliability was assessed in 31 patients who completed the stressometer and the DASS-21 on two occasions 4 weeks apart. RESULTS: Stressometer levels correlated with the DASS-21 stress dimension in both Crohn's disease [CD] (Spearman's rank correlation coefficient [rs] 0.54; p < 0.001) and ulcerative colitis [UC] [rs 0.59; p < 0.001]. Stressometer levels were less closely associated with depression and anxiety [rs range 0.36 to 0.49; all p-values < 0.001]. Stressometer scores correlated with all four Short Health Scale quality of life dimensions in both CD and UC [rs range 0.35 to 0.48; all p-values < 0.001] and with disease activity in Crohn's disease [rs 0.46; p < 0.001] and ulcerative colitis [rs 0.20; p = 0.02]. Responsiveness was confirmed with a test-retest correlation of 0.43 [p = 0.02]. CONCLUSIONS: The stressometer is a simple, valid, and responsive measure of psychological stress in IBD patients and may be a useful patient-reported outcome measure in future IBD clinical and research assessments.
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Colitis Ulcerosa/psicología , Enfermedad de Crohn/psicología , Estrés Psicológico/diagnóstico , Encuestas y Cuestionarios , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Calidad de Vida , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Estrés Psicológico/etiología , Adulto JovenRESUMEN
AIMS: To determine whether specific magnetic resonance enterography (MRE) findings can predict outcome following commencement of antitumor necrosis factor (aTNF) in small bowel Crohn's disease (CD) PATIENTS AND METHODS: This was a single-centre retrospective study of patients with CD who commenced aTNF (infliximab or adalimumab) between 2007 and 2013. Patients who had an MRE within 6 months before commencing aTNF were included. The primary end-point was the need for CD-related surgery. The secondary end-points were time to surgery and time to treatment failure. The relationship between these end-points, clinical variables and specific MRE findings were studied. RESULTS: Four hundred and eighteen patients commenced aTNF for CD during the study period. Seventy-five patients had an MRE within 6 months before commencing aTNF (30 infliximab; 45 adalimumab). The median time from MRE to commencing aTNF was 43 days (IQR 19.5-87 days). Eighteen of 75 (24%) had surgery during a median follow-up of 16.7 months (IQR 9.0-30.1 months). Patients with small bowel stenosis (SBS) on MRE were at a significantly higher risk of requiring surgery: 12/18 (66.7%) versus 6/57 (10.5%) (P<0.001). Time to surgery was significantly shorter in patients with SBS on MRE (P<0.001). In a multivariate analysis, SBS (P<0.0001, hazard ratio 26.45, 95% confidence interval 5.45-128.49) and presence of penetrating complications (P=0.003, hazard ratio 36.53, 95% confidence interval 3.40-393.19) were associated independently with time to surgery. CONCLUSION: SBS and penetrating complications on MRE are associated independently with a need for early surgery and treatment failure in patients commencing aTNF.
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Antiinflamatorios/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Intestino Delgado/efectos de los fármacos , Imagen por Resonancia Magnética/métodos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Distribución de Chi-Cuadrado , Enfermedad de Crohn/inmunología , Enfermedad de Crohn/patología , Enfermedad de Crohn/cirugía , Progresión de la Enfermedad , Femenino , Humanos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Intestino Delgado/inmunología , Intestino Delgado/patología , Intestino Delgado/cirugía , Irlanda , Estimación de Kaplan-Meier , Masculino , Análisis Multivariante , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Insuficiencia del Tratamiento , Factor de Necrosis Tumoral alfa/inmunología , Adulto JovenRESUMEN
BACKGROUND: Body image refers to a person's sense of their physical appearance and body function. A negative body image self-evaluation may result in psychosocial dysfunction. Crohn's disease and ulcerative colitis are associated with disabling features, and body image dissatisfaction is a concern for many patients with inflammatory bowel disease (IBD). However, no study has assessed body image and its comorbidities in patients with IBD using validated instruments. Our aim was to explore body image dissatisfaction in patients with IBD and assess its relationship with biological and psychosocial variables. METHODS: We studied 330 patients (median age, 36 yr; range, 18-83; 169 men) using quantitative and qualitative methods. Patients completed a self-administered questionnaire that included a modified Hopwood Body Image Scale, the Cash Body Image Disturbance Questionnaire, and other validated instruments. Clinical and disease activity data were also collected. RESULTS: Body image dissatisfaction was associated with disease activity (P < 0.001) and steroid treatment (P = 0.03) but not with immunotherapy (P = 0.57) or biological (P = 0.55) therapy. Body image dissatisfaction was also associated with low levels of general (P < 0.001) and IBD-specific (P < 0.001) quality of life, self-esteem (P < 0.001), and sexual satisfaction (P < 0.001), and with high levels of anxiety (P < 0.001) and depression (P < 0.001). Qualitative analysis indicated that patients were concerned about both physical and psychosocial consequences of body image dissatisfaction, including steroid side effects and impaired work and social activities. CONCLUSIONS: Body image dissatisfaction is common in patients with IBD, relates to specific clinical variables and is associated with significant psychological dysfunction. Its measurement is warranted as part of a comprehensive patient-centered IBD assessment.
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Imagen Corporal/psicología , Enfermedades Inflamatorias del Intestino/psicología , Satisfacción del Paciente/estadística & datos numéricos , Calidad de Vida , Trastorno de la Conducta Social/etiología , Estrés Psicológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Emociones , Femenino , Estudios de Seguimiento , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/fisiopatología , Masculino , Persona de Mediana Edad , Pronóstico , Psicometría/métodos , Autoimagen , Índice de Severidad de la Enfermedad , Trastorno de la Conducta Social/psicología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND & AIMS: Administration of infliximab to patients with acute severe ulcerative colitis (ASUC) (rescue therapy) can reduce the rate of early colectomy (within 12 months), but long-term rates of colectomy are the same as those of the pre-biologic era for these patients. The half-life of infliximab is shorter in patients with ASUC than in patients with non-severe UC, so more frequent dosing might be required to produce a therapeutic effect. METHODS: We performed a retrospective analysis of 50 hospitalized patients who received infliximab for steroid-refractory ASUC at a single academic center from September 2005 through 2013. In 2011 an accelerated dosing strategy for infliximab was introduced; we compared outcomes of standard and accelerated dosing regimens. One group of patients (n = 35) were placed on a standard dosing regimen for infliximab and then given the drug at 0, 2, and 6 weeks and then every 8 weeks thereafter. A second group (n = 15) were placed on an accelerated regimen and received 3 induction doses of infliximab within a median period of 24 days. Rates of colectomy were compared between the groups during induction and follow-up periods. RESULTS: There were no differences between groups in median baseline levels of C-reactive protein, albumin, or hemoglobin. The rate of colectomy during induction therapy was significantly lower with the accelerated regimen (6.7%, 1 of 15) than with the standard regimen (40%, 14 of 35) (Fisher exact test, P = .039). The standard regimen was associated with shorter time to colectomy (log-rank test, P = .042). Among patients who completed induction therapy, subsequent need for colectomy was similar between the groups during the follow-up period. Multivariate analysis showed that factors independently associated with successful induction therapy were level of albumin (g/L) when the treatment began (P = .003) and the accelerated dosing regimen (P = .03). CONCLUSIONS: In patients with ASUC, an accelerated infliximab induction strategy reduces the need for early colectomy. An intensified infliximab dosing strategy in response to clinical or laboratory signs of breakthrough inflammation merits consideration in prospective studies.
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Colectomía , Colitis Ulcerosa/tratamiento farmacológico , Factores Inmunológicos/administración & dosificación , Quimioterapia de Inducción/métodos , Infliximab/administración & dosificación , Adulto , Animales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To assess mortality in inflammatory bowel disease (IBD) patients under 65 years of age and to identify the factors related to death in this age group. METHODS. We studied 2570 IBD patients who were diagnosed as having disease before 65 years of age and attended a single tertiary referral center area between 1983 and 2012. Follow-up was censored at 65 years. The causes of death were determined from death certificates obtained from the Irish registry office of births, marriages and deaths. Observed all-cause survival was compared with expected survival of persons of the same age and sex in the general population. Expected survival was obtained from national life tables produced by the central statistics office. Survival estimates were calculated for disease type, disease site, gender, the presence of primary sclerosing cholangitis (PSC), immunomodulator use, biologic therapy use, presence of fistulating disease and prior surgery. RESULTS: Fifty-two deaths were reported in the population younger than 65 years, of which 41 were IBD related. We found little difference in survival in the first 25 years of follow-up, but relative survival decreased in both the Crohn's disease (CD) and ulcerative colitis (UC) cohort thereafter, so that 30-year mortality was excessive in both groups. An adjusted multivariate regression analysis of patients with CD identified PSC as the only predictor of premature mortality (p = 0.003). PSC was also identified as the only independent predictor of mortality in UC patients (p = 0.03). CONCLUSIONS: The presence of PSC poses the greatest risk for mortality in both UC and CD.
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Enfermedades Inflamatorias del Intestino/mortalidad , Adulto , Anciano , Niño , Preescolar , Colangitis Esclerosante/complicaciones , Colangitis Esclerosante/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Irlanda/epidemiología , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND AND AIMS: Many aspects of microscopic colitis remain poorly understood. Our aim was to report a single centre experience with this condition. METHODS: Two hundred and twenty-two patients (52 male, 170 female; median age 64 years; range 32-90) diagnosed between 1993 and 2010 were studied. Medical notes were reviewed, and data on age, gender, clinical features, history of autoimmune diseases, medication use, cigarette smoking, histology and outcome were collected. RESULTS: There were 99 cases of lymphocytic and 123 of collagenous colitis. Diarrhoea was almost invariably present (98 %) while abdominal pain (24 %), weight loss (10 %), faecal incontinence (8 %) and blood PR (5 %) were also described. Twenty-eight percent had concomitant autoimmune diseases, most commonly coeliac disease. Patients were taking a variety of medications at diagnosis thought to be associated with microscopic colitis including NSAIDs (22 %), aspirin (19 %), statins (15 %), proton pump inhibitors (19 %) and SSRIs (10 %) at diagnosis. Prior to the widespread use of budesonide in our institution, 33 % of patients required two or more medications during therapy compared to 15 % following the introduction of budesonide (p = 0.001). Thirty-eight percent of patients achieved spontaneous remission with either no treatment or simple anti-diarrhoeals. Using a multivariate model, the only factor associated with spontaneous remission was male gender (RR 1.9; 95 % CI 1.0-3.6; p = 0.04). Two patients had refractory microscopic colitis; one required a colectomy while a more recent case has responded to anti-TNFα therapy. CONCLUSION: Microscopic colitis is predominantly a benign and self-limiting disorder. The introduction of budesonide has revolutionised treatment of this lesser studied inflammatory bowel disease.
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Colitis Microscópica/tratamiento farmacológico , Colitis Microscópica/etiología , Dolor Abdominal/etiología , Anciano , Antiinflamatorios/uso terapéutico , Budesonida/uso terapéutico , Colitis Microscópica/complicaciones , Colitis Microscópica/patología , Diarrea/etiología , Incontinencia Fecal/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Remisión Espontánea , Estudios Retrospectivos , Resultado del Tratamiento , Pérdida de PesoRESUMEN
BACKGROUND: Body image refers to a persons' sense of their own physical appearance. This can be negatively influenced by a number of factors including disease states and treatments. Inflammatory bowel disease (IBD) carries a distinct psychosocial and a physical burden, but body image has not been formally assessed in patients with IBD, nor is there a validated body image questionnaire. Our aim was to assess and validate a body image questionnaire for patients with IBD. METHODS: Three hundred thirty-eight ambulatory patients (median age, 36; 174 male) completed a questionnaire that included the Hopwood body image scale adapted from the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Study Group. Data from another scale, the Cash Body Image Disturbance Questionnaire, were also collected in addition to demographic and clinical data. RESULTS: Factor analysis resulted in a single factor solution explaining 65% of the variance. Internal consistency of the body image scale was demonstrated with a Cronbach alpha of 0.93. Convergent validity was established with a correlation coefficient of 0.64 (P < 0.001) with the Cash Body Image Disturbance Questionnaire. Females (P < 0.001) and those who had undergone either stoma or nonstoma forming surgery experienced more body image dissatisfaction (P = 0.002), indicating predictive validity. Reliability was confirmed with a test-retest correlation of 0.82 (P < 0.001). CONCLUSIONS: The modified body image scale is a valid tool for assessing body image in patients with IBD.
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Imagen Corporal/psicología , Emociones/fisiología , Enfermedades Inflamatorias del Intestino/psicología , Satisfacción del Paciente/estadística & datos numéricos , Psicometría/métodos , Calidad de Vida , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVE: To examine the association between single-nucleotide polymorphisms (SNPs) in CTGF (connective tissue growth factor) and patient outcomes after terminal ileal resection for Crohn's disease. BACKGROUND: The primary indication for intestinal resection in Crohn's disease is fibrostenotic terminal ileal disease. CTGF is a cytokine overexpressed in the intestine of patients with Crohn's disease that influences outcomes in other disease processes. METHODS: DNA was extracted from formalin-fixed, paraffin-embedded tissue from 147 patients with Crohn's disease who had undergone terminal ileal resection between 1981 and 2009. Genotyping was performed for 4 CTGF SNPs (rs9402373, rs12526196, rs6918698, and rs9399005), which modulate nuclear factor binding and CTGF production, and a smad3 SNP (rs17293632) involved in the CTGF pathway. Patients were phenotyped using the Montreal Disease Classification. RESULTS: Sixty-seven of 147 patients (45.6%) were male; the mean age at diagnosis was 30.3 ± 12.6 years and the mean follow-up duration was 8.3 ± 7.1 years. Genotype-phenotype analysis demonstrated that the rs6918698GG genotype was associated with an older age of disease onset [>40 years; 30.6% vs 13.2%; odds ratio (OR): 2.891; 95% confidence interval (CI): 1.170-7.147). The rs9402373CC genotype was positively associated with type B1 disease (50.7% vs 26.3%; OR: 2.876; 95% CI: 1.226-6.743) and negatively associated with B2 disease (37.0% vs 65.0%; OR: 0.317; 95% CI: 0.144-0.699). None of the 5 SNPs assessed influenced clinical or surgical recurrence of Crohn's disease after intestinal resection. On multivariate analysis, male sex odds ratio (OR): 0.235; 95% CI: 0.073-0.755; P = 0.015] and never having smoked tobacco (OR: 0.249; 95% CI: 0.070-0.894; P = 0.033) reduced the risk, whereas having a prior appendectomy increased the risk (OR: 5.048; 95% CI: 1.632-15.617; P = 0.005) of surgical recurrence. CONCLUSIONS: These data implicate the rs6918698GG genotype with an age of disease onset of greater than 40 years in Crohn's disease whereas the rs9402373CC genotype is associated with a nonstricturing, nonpenetrating disease phenotype. CTGF SNPs do not influence the rate of recurrence after terminal ileal resection for Crohn's disease.
Asunto(s)
Factor de Crecimiento del Tejido Conjuntivo/genética , Enfermedad de Crohn/genética , Enfermedad de Crohn/cirugía , Polimorfismo de Nucleótido Simple , Adulto , Edad de Inicio , Femenino , Genotipo , Humanos , Masculino , Fenotipo , Recurrencia , Estudios Retrospectivos , Proteína smad3/genéticaRESUMEN
BACKGROUND: Disease related knowledge may be associated with quality of life, coping skills and medication adherence. However, little is known of cross-cultural variations regarding inflammatory bowel disease knowledge or sources of information and no study has assessed knowledge in diverse European IBD populations. AIM: To assess sources of information and patient knowledge in Irish and German inflammatory bowel disease patients. METHODS: Three hundred and three disease, gender, age and education matched German and Irish patients completed a previously validated knowledge questionnaire. Additional data were collected on age, gender, education, disease type and duration, family history, smoking habits, medication use, previous surgery and quality of life. RESULTS: German patients obtained knowledge from a wider range of sources than Irish patients (p<0.001), most notably from the internet (p<0.001), newspapers and magazines (p=0.002). Both cohorts answered a similar number of questions correctly (Irish, mean 4.4 questions (Standard deviation (S.D.) 2.4); German, mean 4.3 (S.D. 2.2); p=0.67). In addition, both nationalities answered "don't know" to a similar number of questions (Irish, mean 3.3 (S.D. 3.1); German, mean 2.7 (S.D. 2.8); p=0.12) while Irish patients answered slightly fewer questions wrongly (Irish, mean 2.4 (S.D. 1.8); German, mean 3.1 (S.D. 1.9); p=0.002). A multivariate analysis included only Crohn's disease, female gender, young age and higher educational status as being significantly and independently associated with knowledge. CONCLUSIONS: Our data suggest few differences between German and Irish IBD patients, despite cultural and linguistic differences, with regard to disease related knowledge of IBD.
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Conocimientos, Actitudes y Práctica en Salud , Enfermedades Inflamatorias del Intestino/psicología , Conducta en la Búsqueda de Información , Factores de Edad , Comparación Transcultural , Escolaridad , Femenino , Alemania , Humanos , Internet , Irlanda , Masculino , Periódicos como Asunto , Educación del Paciente como Asunto , Publicaciones Periódicas como Asunto , Calidad de Vida , Factores Sexuales , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Magnetic resonance enterography (MRE) is a relatively new imaging modality that involves small bowel distension with orally administered fluid. Few studies have assessed its impact on patient management. AIM: The aim of this study was to determine whether MRE influenced the management of patients with established small bowel Crohn's disease (CD). MATERIALS AND METHODS: From a prospectively maintained database of patients with inflammatory bowel disease, we identified patients with small bowel CD who underwent MRE between January 2007 and December 2010. The results of the MRE and subsequent changes in patient management within 1 month were evaluated. RESULTS: Thirty women and 27 men with CD were included. Seven patients (12%) had a normal MRE. Forty-two of 57 (74%) patients had a change in management, and 41/50 (82%) patients with an abnormal MRE had changes in management (P<0.0008). After MRE, 20/42 (47%) patients had surgery and 22/42 (53%) had changes in medical treatment. Patients with stricturing disease had more surgical intervention (P=0.02), and patients with active disease on MRE had more medical intervention (P=0.0001). Patients with two or more abnormalities on MRE had more surgery compared with medical therapy (P=0.02). CONCLUSION: The majority of patients with small bowel CD had a change in management as a result of the MRE. Because of its high clinical impact on patient management, MRE should become one of the preferred methods of small bowel evaluation in CD. Specific MRE findings may help to stratify treatment options, however, further work is required to validate this.
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Enfermedad de Crohn/diagnóstico , Intestino Delgado/patología , Imagen por Resonancia Magnética/métodos , Adolescente , Adulto , Anciano , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/cirugía , Femenino , Humanos , Obstrucción Intestinal/diagnóstico , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Intestino Delgado/cirugía , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
INTRODUCTION: Adalimumab is a recombinant human IgG1 monoclonal antibody to TNF-alpha. There are limited data with regard to its efficacy in ulcerative colitis. We report experience of adalimumab in ulcerative colitis in a single centre with a focus on the ability of this agent to maintain response and avoid colectomy in the medium to long-term. METHODS: Twenty-three ulcerative colitis patients (mean age 32 years; 7 female) who received adalimumab were identified from a prospectively maintained database of over 2700 IBD patients. The primary study endpoint was treatment failure defined as discontinuation of adalimumab due to lack of efficacy, as defined by requiring an alternative maintenance therapy or colectomy, or intolerance. Colectomy rate was recorded as a secondary endpoint. RESULTS: Most patients (96%) had received immunosuppressants prior to adalimumab therapy (infliximab 20/23 87%). Sixteen of 23 patients (70%) discontinued adalimumab. Six primary failures, 8 secondary loss of response, one had unacceptable side effects and one discontinued treatment after 6 months but remains in remission. Overall estimated cumulative treatment failure rates at 6, 12 and 24 months were 50%, 65% and 72% respectively. Median follow-up in patients continuing adalimumab is 23 months (IQR 17-31 months). Treatment failure was unrelated to patient age, gender, disease extent, smoking status or CRP. Colectomy free survival was 59% at 2 years. No patient experienced a major adverse event. CONCLUSION: Adalimumab shows some efficacy as a maintenance strategy in Ulcerative Colitis, but only a limited proportion of patients remain well on continued treatment at 2 years.
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Antiinflamatorios no Esteroideos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Adalimumab , Adulto , Anciano , Antiinflamatorios no Esteroideos/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Colectomía , Colitis Ulcerosa/cirugía , Femenino , Estudios de Seguimiento , Humanos , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Insuficiencia del TratamientoRESUMEN
BACKGROUND AND AIMS: There is a high rate of stricturing post-operative recurrence in Crohn's disease (CD) particularly at sites of surgical anastomosis, and over 50% of these patients will require a repeat resection. Endoscopic dilatation of anastomotic strictures is an alternative to surgical resection in selected patients. We aimed to evaluate the safety and long term efficacy of endoscopic balloon dilatation of symptomatic anastomotic strictures in CD. METHODS: Retrospective analysis of a prospectively maintained inflammatory bowel disease database of patients attending a single academic centre (n=1244 patients with CD) who underwent dilatation. RESULTS: Fifty-five dilatations were performed in 31 patients (mean age 43 ± SD 12, 47% female). Median follow-up period was 46 months (IQR 14-62). Ninety percent of patients had successful initial dilatation and no complications occurred. Six (21%) avoided further dilatations or surgery in the follow-up period. Stricture recurrence was detected in 22 patients; 15 (54%) patients had repeat dilatations and seven (25%) went straight to surgery. Eight (28%) patients were managed with repeat dilatations of the stricture (median dilatations=2 range 2-6) and seven (25%) required surgery despite repeat dilatations. Median time from first dilatation to repeat surgery was 14.5 months (IQR 3-28) and to repeat dilatation was 13.8 months (IQR 4-28). There was no difference in immunomodulator use, biologic use and smoking status between the groups requiring surgery versus dilatation only. CONCLUSION: Endoscopic balloon dilatation of anastomotic strictures is safe and effective in providing symptomatic relief in CD patients. Forty-five percent of patients had a sustained response to single/serial balloon dilatation with avoidance of further surgical resection for a median interval of 46 months. Post-operative medical therapy and smoking status did not predict requirement for recurrent dilatation or surgery.