RESUMEN
OBJECTIVES: Surveillance colonoscopy is thought to prevent colorectal cancer (CRC) in patients with long-standing colonic IBD, but data regarding the frequency of surveillance and the findings thereof are lacking. Our aim was to determine whether consecutive negative surveillance colonoscopies adequately predict low neoplastic risk. DESIGN: A multicentre, multinational database of patients with long-standing IBD colitis without high-risk features and undergoing regular CRC surveillance was constructed. A 'negative' surveillance colonoscopy was predefined as a technically adequate procedure having no postinflammatory polyps, no strictures, no endoscopic disease activity and no evidence of neoplasia; a 'positive' colonoscopy was a technically adequate procedure that included at least one of these criteria. The primary endpoint was advanced colorectal neoplasia (aCRN), defined as high-grade dysplasia or CRC. RESULTS: Of 775 patients with long-standing IBD colitis, 44% (n=340) had >1 negative colonoscopy. Patients with consecutive negative surveillance colonoscopies were compared with those who had at least one positive colonoscopy. Both groups had similar demographics, disease-related characteristics, number of surveillance colonoscopies and time intervals between colonoscopies. No aCRN occurred in those with consecutive negative surveillance, compared with an incidence rate of 0.29 to 0.76/100 patient-years (P=0.02) in those having >1 positive colonoscopy on follow-up of 6.1 (P25-P75: 4.6-8.2) years after the index procedure. CONCLUSION: Within this large surveillance cohort of patients with colonic IBD and no additional high-risk features, having two consecutive negative colonoscopies predicted a very low risk of aCRN occurrence on follow-up. Our findings suggest that longer surveillance intervals in this selected population may be safe.
Asunto(s)
Colitis/patología , Neoplasias del Colon/patología , Colonoscopía , Lesiones Precancerosas/patología , Adulto , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Vigilancia de la Población , Valor Predictivo de las Pruebas , Factores de RiesgoRESUMEN
BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC, termed PSC-IBD) are at increased risk for colorectal cancer, but their risk following a diagnosis of low-grade dysplasia (LGD) is not well described. We aimed to determine the rate of advanced colorectal neoplasia (aCRN), defined as high-grade dysplasia and/or colorectal cancer, following a diagnosis of indefinite dysplasia or LGD in this population. METHODS: We performed a retrospective, longitudinal study of 1911 patients with colonic IBD (293 with PSC and 1618 without PSC) who underwent more than 2 surveillance colonoscopies from 2000 through 2015 in The Netherlands or the United States (9265 patient-years of follow-up evaluation). We collected data on clinical and demographic features of patients, as well as data from each surveillance colonoscopy and histologic report. For each surveillance colonoscopy, the severity of active inflammation was documented. The primary outcome was a diagnosis of aCRN during follow-up evaluation. We also investigated factors associated with aCRN in patients with or without a prior diagnosis of indefinite dysplasia or LGD. RESULTS: Patients with PSC-IBD had a 2-fold higher risk of developing aCRN than patients with non-PSC IBD. Mean inflammation scores did not differ significantly between patients with PSC-IBD (0.55) vs patients with non-PSC IBD (0.56) (P = .89), nor did proportions of patients with LGD (21% of patients with PSC-IBD vs 18% of patients with non-PSC IBD) differ significantly (P = .37). However, the rate of aCRN following a diagnosis of LGD was significantly higher in patients with PSC-IBD (8.4 per 100 patient-years) than patients with non-PSC IBD (3.0 per 100 patient-years; P = .01). PSC (adjusted hazard ratio [aHR], 2.01; 95% CI, 1.09-3.71), increasing age (aHR 1.03; 95% CI, 1.01-1.05), and active inflammation (aHR, 2.39; 95% CI, 1.63-3.49) were independent risk factors for aCRN. Dysplasia was more often endoscopically invisible in patients with PSC-IBD than in patients with non-PSC IBD. CONCLUSIONS: In a longitudinal study of almost 2000 patients with colonic IBD, PSC remained a strong independent risk factor for aCRN. Once LGD is detected, aCRN develops at a higher rate in patients with PSC and is more often endoscopically invisible than in patients with only IBD. Our findings support recommendations for careful annual colonoscopic surveillance for patients with IBD and PSC, and consideration of colectomy once LGD is detected.
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Colangitis Esclerosante/complicaciones , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Enfermedades Inflamatorias del Intestino/complicaciones , Adolescente , Adulto , Colonoscopía , Femenino , Histocitoquímica , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Estudios Retrospectivos , Medición de Riesgo , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND & AIMS: Patients with colitis have an increased risk of colorectal cancer, compared with persons without colitis. Many studies have shown chromoendoscopy (CE) to be superior to standard methods of detecting dysplasia in patients with colitis at index examination. We performed a prospective, longitudinal study to compare standard colonoscopy vs CE in detecting dysplasia in patients with inflammatory bowel diseases in a surveillance program. METHODS: We analyzed data from 68 patients (44 men, 24 women) diagnosed with ulcerative colitis (n = 55) or Crohn's disease (n = 13) at Mount Sinai Medical Center from September 2005 through October 2011. The patients were followed from June 2006 through October 2011 (median, 27.8 months); each patient was analyzed by random biopsy, targeted white light examination (WLE), and CE. Specimens were reviewed by a single blinded pathologist. The 3 methods were compared by using the generalized estimating equations method, and the odds ratios (ORs) for detection of dysplasia were calculated (primary outcome). Time to colectomy was analyzed by using the Cox model. RESULTS: In the 208 examinations conducted, 44 dysplastic lesions were identified in 24 patients; 6 were detected by random biopsy, 11 by WLE, and 27 by CE. Ten patients were referred for colectomy, and no carcinomas were found. At any time during the study period, CE (OR, 5.4; 95% confidence interval [CI], 2.9-9.9) and targeted WLE (OR, 2.3; 95% CI, 1.0-5.3) were more likely than random biopsy analysis to detect dysplasia. CE was superior to WLE (OR, 2.4; 95% CI, 1.4-4.0). Patients identified as positive for dysplasia were more likely to need colectomy (hazard ratio, 12.1; 95% CI, 3.2-46.2). CONCLUSIONS: In a prospective study of 68 patients with inflammatory bowel diseases, CE was superior to random biopsy or WLE analyses in detecting dysplasia in patients with colitis during an almost 28-month period. A negative result from CE examination was the best indicator of a dysplasia-free outcome, whereas a positive result was associated with earlier referral for colectomy.
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Colitis/complicaciones , Neoplasias Colorrectales/diagnóstico , Endoscopía/métodos , Enfermedades Inflamatorias del Intestino/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
Serrated colorectal polyps, which, besides hyperplastic polyps, comprise sessile serrated adenomas/polyps and traditional serrated adenomas, are presumptive precursors of at least 20% of sporadic colorectal carcinomas; however, their significance in patients with inflammatory bowel disease is unclear. We retrospectively evaluated 78 serrated polyps, removed over a 14-year period from 6602 inflammatory bowel disease patients undergoing endoscopic surveillance, with respect to morphologic, clinicopathologic, and molecular features, and compared rates of advanced neoplasia (high-grade dysplasia and carcinoma) development following the index serrated polyp diagnosis to reference inflammatory bowel disease cohorts without serrated polyps. Serrated polyps negative for dysplasia, which morphologically resembled sporadic sessile serrated adenoma/polyps, occurred mainly in females, in the proximal colon, and contained BRAF mutations. Serrated polyps with low-grade dysplasia resembled sporadic traditional serrated adenomas and occurred mainly in males, in the distal colon, and contained KRAS mutations. Serrated polyps indefinite for dysplasia were morphologically heterogeneous, but similar to serrated polyps positive for low-grade dysplasia with respect to male predominance, left-sided location, and KRAS mutation rates. Rates of prevalent neoplasia associated with serrated polyps positive for low-grade dysplasia, indefinite for dysplasia, and negative for dysplasia were 76, 39, and 11%, respectively (P<0.001). Actuarial 10-year rates of incident advanced neoplasia after an initial diagnosis of serrated polyp positive for low-grade dysplasia, indefinite for dysplasia, and negative for dysplasia were 17, 8, and 0%, respectively, the first and last being significantly different (P=0.02) and comparable to those of corresponding reference populations of inflammatory bowel disease patients with and without low-grade dysplasia at baseline, respectively. We conclude that in serrated polyps from inflammatory bowel disease patients, dysplasia grade correlates with morphology, sex, anatomic location, BRAF and KRAS mutation status, prevalent conventional neoplasia, and rates of advanced neoplasia development.
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Pólipos del Colon/complicaciones , Pólipos del Colon/patología , Enfermedades Inflamatorias del Intestino/complicaciones , Adulto , Anciano , Pólipos del Colon/genética , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Femenino , Humanos , Incidencia , Enfermedades Inflamatorias del Intestino/patología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Estudios RetrospectivosRESUMEN
OBJECTIVE: Early readmission rates are becoming an integral measure of the quality of care for hospitalized patients with chronic diseases. The incidence and predictors of early readmission in patients with inflammatory bowel disease (IBD) are uncertain. Risk factors for readmission over the first few weeks may differ from those that influence re-hospitalization at later time points. We examined the incidence and predictors of both 30-day and 90-day readmissions among ulcerative colitis (UC) patients. MATERIALS AND METHODS: A retrospective, cohort study was performed including all severe UC patients admitted to a tertiary-care hospital between January 2007 and December 2011. All-cause readmissions to the medical or surgical service within 30 and 90 days were recorded to allow the calculation of early readmission rates. We used multiple logistic regression to analyze demographic, hospital-related, general medical and IBD-specific factors as potential risk factors for readmission. RESULTS: There were a total of 229 patients discharged following hospitalization for severe UC. The 30- and 90-day readmission rates were 11.7% and 20.5%, respectively. Forty-seven percent of early readmissions were for colectomy. In the 30-day analysis, only the presence of extensive colitis (odds ratio 3.59; 95% confidence interval [CI] 1.41-9.13) compared with left-sided disease was independently associated with readmission. Extensive colitis (3.09, 95% CI 1.33-7.08), albumin on admission (0.56, 0.31-0.99) and being admitted to a housestaff service (2.87, 95% CI 1.14-6.54), were independent predictors of readmission at 90 days. CONCLUSIONS: Early readmission is common in IBD. Independent risk factors for early readmission included extensive colitis, admission albumin, and being admitted to a housestaff service.
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Colectomía/métodos , Colitis Ulcerosa/terapia , Hospitalización/estadística & datos numéricos , Readmisión del Paciente/estadística & datos numéricos , Adulto , Colitis Ulcerosa/complicaciones , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Centros de Atención Terciaria , Adulto JovenRESUMEN
BACKGROUND: Inflammatory bowel disease (IBD) patients are at an increased risk of thrombosis, particularly when hospitalized. Several clinical practice guidelines now recommend pharmacologic prophylaxis for hospitalized ulcerative colitis and Crohn's disease patients. It is unclear to what extent gastroenterologists are aware of these recommendations and whether they are administering pharmacologic venous thromboembolism (VTE) prophylaxis appropriately. Our aim was to explore current practice of VTE prophylaxis in hospitalized IBD patients in the United States. METHODS: A survey was mailed electronically to gastroenterologists whose electronic mail address was listed in the American College of Gastroenterology (ACG) database. This survey included clinical vignettes outlining scenarios for consideration of VTE prophylaxis. RESULTS: A total of 6227 surveys were sent to gastroenterologists nationwide, and 591 physicians chose to participate (response rate 9.5%). Respondents (80.6%) believed that hospitalized IBD patients have a higher risk of VTE than other inpatients. A total of 29.1% were unaware of any recommendations addressing pharmacologic prophylaxis included in ACG IBD guidelines and 34.6% would give pharmacologic VTE prophylaxis to a hospitalized patient with severe ulcerative colitis. Heparin VTE prophylaxis use was associated with gastroenterologists who indicated that their practices comprised more than 50% of patients with IBD (P=0.0001), being a physician at an academic hospital (P=0.0001) and providers having less than 5 years practice experience (P=0.003). CONCLUSIONS: Despite reasonable awareness of the increased risk of thrombosis in hospitalized IBD patients, many US gastroenterologists may not follow clinical practice guidelines and use pharmacologic VTE prophylaxis.
Asunto(s)
Anticoagulantes/uso terapéutico , Gastroenterología , Heparina/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Pacientes Internos , Pautas de la Práctica en Medicina , Tromboembolia Venosa/prevención & control , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Encuestas de Atención de la Salud , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/prevención & control , Guías de Práctica Clínica como Asunto , Encuestas y Cuestionarios , Resultado del Tratamiento , Estados Unidos , Tromboembolia Venosa/etiología , Recursos HumanosRESUMEN
BACKGROUND: Observational studies have described racial differences in inflammatory bowel disease (IBD) genetics, clinical manifestations, and outcomes. Whether race impacts response to biologics in IBD is unclear. We conducted a post hoc analysis of phase 2 and 3 randomized clinical trials in ulcerative colitis to evaluate the effect of race on response to golimumab. METHODS: We analyzed pooled individual-level data from induction and maintenance trials of golimumab through the Yale Open Data Access Project. The primary outcome was clinical response. Secondary outcomes were clinical remission and endoscopic healing. Multivariable logistic regression was performed comparing White vs racial minority groups (Asian, Black, or other race), adjusting for potential confounders. RESULTS: There were 1006 participants in the induction (18% racial minority) and 783 participants in the maintenance (17% racial minority) trials. Compared with White participants, participants from racial minority groups had significantly lower clinical response (adjusted odds ratio [aOR], 0.43; 95% confidence interval [CI], 0.28-0.66), clinical remission (aOR, 0.41; 95% CI, 0.22-0.77), and endoscopic healing (aOR, 0.48; 95% CI, 0.31-0.74) at week 6. Participants from racial minority groups also had significantly lower clinical remission (aOR, 0.46; 95% CI, 0.28-0.74) and endoscopic healing (aOR, 0.63; 95% CI, 0.41-0.96) at week 30. There were no racial differences in placebo response rates. CONCLUSIONS: Ulcerative colitis participants from racial minority groups were less likely to achieve clinical response, clinical remission, and endoscopic healing with golimumab compared with White participants in induction and maintenance trials. Further studies are needed to understand the impact of race on therapeutic response in IBD.
Racial disparities exist in inflammatory bowel disease, but the influence of race on response to biologic therapy is unclear. In pooled analysis of golimumab clinical trials, participants from racial minority groups were less likely to achieve clinical efficacy compared with White participants.
Asunto(s)
Colitis Ulcerosa , Enfermedades Inflamatorias del Intestino , Humanos , Anticuerpos Monoclonales/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Inducción de RemisiónRESUMEN
Patients with ulcerative colitis and Crohn's disease are at increased risk for developing colorectal cancer (CRC). Chronic inflammation is believed to promote carcinogenesis. The risk for colon cancer increases with the duration and anatomic extent of colitis and presence of other inflammatory disorders (such as primary sclerosing cholangitis), whereas it decreases when patients take drugs to reduce inflammation (such as mesalamine and steroids). The genetic features that lead to sporadic CRC-chromosome instability, microsatellite instability, and DNA hypermethylation-also occur in colitis-associated CRC. Unlike the normal colonic mucosa, cells of the inflamed colonic mucosa have these genetic alterations before there is any histologic evidence of dysplasia or cancer. The reasons for these differences are not known, but oxidative stress is likely to be involved. Reactive oxygen and nitrogen species produced by inflammatory cells can affect regulation of genes that encode factors that prevent carcinogenesis (such as p53, DNA mismatch repair proteins, and DNA base excision-repair proteins), transcription factors (such as nuclear factor-κB), or signaling proteins (such as cyclooxygenases). Administration of agents that cause colitis in healthy rodents or genetically engineered, cancer-prone mice accelerates development of colorectal tumors. Mice genetically prone to inflammatory bowel disease also develop CRC, especially in the presence of bacterial colonization. Individual components of the innate and adaptive immune response have also been implicated in carcinogenesis. These observations offer compelling support for the role of inflammation in colon carcinogenesis.
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Colitis Ulcerosa/complicaciones , Neoplasias del Colon/etiología , Enfermedad de Crohn/complicaciones , Inmunidad Adaptativa , Animales , Antiinflamatorios/uso terapéutico , Infecciones Bacterianas/complicaciones , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Neoplasias del Colon/patología , Neoplasias del Colon/fisiopatología , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/metabolismo , Tracto Gastrointestinal/microbiología , Humanos , Inmunidad Innata , Estrés Oxidativo , Factores de RiesgoRESUMEN
BACKGROUND & AIMS: Multiple randomized controlled trials (RCTs) have been conducted to determine therapeutic efficacy of the biological agents for the inflammatory bowel diseases (IBD). However, the external validity of findings from RCTs might be compromised by their stringent selection criteria. We investigated the proportion of patients encountered during routine clinical practice who would qualify for enrollment into a pivotal RCT of biological agents for IBD. METHODS: We performed a retrospective cohort study of adult patients with moderate-severe IBD who presented to a tertiary referral center. Inclusion and exclusion criteria were extracted from published RCTs of biologics approved by the Food and Drug Administration and applied to the study population. RESULTS: Only 31.1% of 206 patients with IBD (34% with Crohn's disease [CD], 26% with ulcerative colitis) would have been eligible to participate in any of the selected RCTs. Patients would have been excluded because they had stricturing or penetrating CD, took high doses of steroids, had comorbidities or prior exposure to biologics, or received topical therapies. Of the trial-ineligible patients with ulcerative colitis, 23.3% had colectomies, and 31.7% received infliximab, with a 63.2% response rate. Approximately half (49.4%) of the 82 trial-ineligible patients with CD received biological therapies, with lower response rates (60%) than trial-eligible patients (89%; P = .03). CONCLUSIONS: Most patients with moderate-severe IBD evaluated in an outpatient practice would not qualify for enrollment in a pivotal RCT of biological reagents; this finding raises important questions about their therapeutic efficacy beyond the clinical trial populations. Additional evaluation of the transparency of RCT design and selection criteria is needed to determine whether trial results can be generalized to the population.
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Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos adversos , Ensayos Clínicos Controlados como Asunto , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , HumanosRESUMEN
BACKGROUND: The role of intravenous (IV) cyclosporine in severe Crohn's colitis (CC) is poorly studied. AIM: Our primary aim was to determine the in-hospital colonic resection rate in patients with severe CC who received IV cyclosporine, and the potential predictors of resection among these patients. METHODS: An inpatient pharmacy query of all patients who received IV cyclosporine at Mount Sinai Medical Center for 12.5 years after January 1, 1996 was reviewed. Patients with CC or indeterminate colitis favoring Crohn's were included and their medical records were reviewed. Subsequent need for colonic surgery was assessed. A Kaplan-Meier plot with log-rank testing was performed to determine the rate of colonic surgery avoidance. Forward stepwise logistic regression was performed to determine independent predictors of surgery. RESULTS: Forty-eight patients met our inclusion criteria. Prior thiopurine and anti-tumor necrosis factor (anti-TNF) use was 85% and 69%, respectively. The median follow-up time was 12 months (range, 1 to 60 mo). 12.5% of patients required colonic resection during their admission for IV cyclosporine. Anti-TNF use in the 4 weeks preceding IV cyclosporine was the only predictor of surgery in this setting (P=0.05). The cumulative colonic surgery avoidance rate was 72±13% at 6 months and 59±15% at 12 months. CONCLUSIONS: The use of IV cyclosporine resulted in a low rate of in-hospitalization colonic surgery among CC patients with severe disease, the majority of whom previously failed anti-TNFs and thiopurines.
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Colectomía/estadística & datos numéricos , Colitis/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Ciclosporina/uso terapéutico , Fármacos Gastrointestinales/uso terapéutico , Administración Intravenosa , Adulto , Colectomía/métodos , Colitis/fisiopatología , Colitis/cirugía , Colon/cirugía , Enfermedad de Crohn/fisiopatología , Enfermedad de Crohn/cirugía , Ciclosporina/administración & dosificación , Femenino , Fármacos Gastrointestinales/administración & dosificación , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Recommendations for venous thromboembolism (VTE) prophylaxis in patients with inflammatory bowel disease (IBD) can be refined by incorporating patient-specific risk factors. OBJECTIVES: To determine the risk of deep venous thrombosis (DVT) and pulmonary embolism (PE) in children and adults with Crohn's disease and ulcerative colitis and evaluate whether this risk varies by age and/or presence of other risk factors. METHODS: We performed a cohort study using Danish administrative data. Incidence rates of DVT and PE were calculated among patients with IBD and an age- and gender-matched comparison population and compared using Cox proportional hazards regression. We performed additional analyses stratifying by age, gender and disease type and restricting outcomes to unprovoked events (occurring without known malignancy, surgery, fracture/trauma or pregnancy). We next performed a nested case-control study to adjust for additional co-morbidities (congestive heart failure, diabetes, myocardial infarction and stroke) and the use of hormone replacement and antipsychotic medications. RESULTS: The study included 49,799 patients with IBD (14,211 Crohn's disease, 35,229 ulcerative colitis) and 477,504 members of the general population. VTE risk was elevated in patients with IBD (HR=2.0 (95% CI 1.8 to 2.1) for total events, HR=1.6 (95% CI 1.5 to 1.8) for unprovoked events). Although the incidence of VTE increased with age, the RR was higher in younger patients. Among those ≤ 20 years old, HRs were 6.0 (95% CI 2.5 to 14.7) for DVT and 6.4 (95% CI 2.0 to 20.3) for PE. After further adjusting for co-morbidity and medication use in the case-control analysis, ORs for all events remained in the 1.5-1.8 range. DISCUSSION: Patients with IBD have twice the incidence of PE or DVT as does the general population. This risk persisted after taking into account other VTE risk factors. Relative risks were particularly high at young ages, though actual incidence increased with age. These findings can further inform risk-benefit analysis of VTE prophylaxis.
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Enfermedades Inflamatorias del Intestino/complicaciones , Tromboembolia/etiología , Adolescente , Adulto , Distribución por Edad , Anciano , Niño , Preescolar , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/epidemiología , Dinamarca/epidemiología , Métodos Epidemiológicos , Femenino , Humanos , Lactante , Recién Nacido , Enfermedades Inflamatorias del Intestino/epidemiología , Masculino , Persona de Mediana Edad , Embolia Pulmonar/epidemiología , Embolia Pulmonar/etiología , Distribución por Sexo , Tromboembolia/epidemiología , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología , Adulto JovenRESUMEN
OBJECTIVES: There remains controversy regarding the efficacy of thiopurine analogs (azathioprine (AZA) and 6-mercaptopurine (6-MP)), methotrexate (MTX), and cyclosporine for the treatment of inflammatory bowel disease (IBD). We performed an updated systematic review of the literature to clarify the efficacy of immunosuppressive therapy at inducing remission and preventing relapse in ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Only parallel group randomized controlled trials (RCTs) were considered eligible. Studies with adult IBD patients receiving immunosuppressive therapy compared with placebo for at least 14 days and up to 17 weeks for active disease, or at least 6 months in quiescent disease were analyzed. Two reviewers independently assessed eligibility and extracted data. The primary outcome was remission or relapse using an intention-to-treat analysis. The data were summarized using relative risk (RR) and pooled using a random effects model. RESULTS: Data on MTX and cyclosporine in IBD were limited although there were some data to support the use of intramuscular MTX in CD but not UC. There were five trials of AZA/6-MP in 380 active CD patients and there was no significant effect of therapy inducing remission (RR=0.87; 95% confidence interval (CI)=0.71-1.06). In quiescent CD, there were two trials involving 198 patients with no significant benefit of active therapy preventing relapse compared with placebo (RR=0.64; 95% CI=0.34-1.23). There were, however, three additional AZA withdrawal trials in 163 patients that indicated continuing medication did prevent relapse (RR=0.39; 95% CI=0.21-0.74). There were two AZA RCTs in 130 active UC patients that suggested a trend for benefit of therapy, but this did not reach statistical significance (RR=0.85; 95% CI=0.71-1.01). In quiescent UC, there were three trials involving 127 patients and there was a statistically significant benefit of AZA preventing relapse (RR=0.60; 95% CI=0.37-0.95). CONCLUSIONS: Most evidence relates to AZA/6-MP where there is no statistically significant benefit at inducing remission in active CD and UC. Thiopurine analogs may prevent relapse in quiescent UC and CD. However, there is a paucity of data for immunosuppressive therapy in IBD and more research is needed.
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Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Azatioprina/uso terapéutico , Ciclosporina/uso terapéutico , Humanos , Inmunosupresores/administración & dosificación , Inyecciones Intramusculares , Mercaptopurina/uso terapéutico , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Inducción de Remisión/métodos , Prevención Secundaria , Insuficiencia del TratamientoRESUMEN
The etiology of inflammatory bowel disease (IBD) is unknown but may relate to an unidentified bacterial pathogen or an immunological reaction to gut microbiota. Antibiotics have therefore been proposed as a therapy for Crohn's disease (CD) and ulcerative colitis (UC) to induce remission in active disease to prevent relapse. Current data are conflicting and we therefore conducted a systematic review of randomized controlled trials (RCTs) evaluating antibiotics in IBD. Only parallel group RCTs were considered eligible. Studies with adult patients receiving any dose of therapy for at least 7 days and up to 16 weeks for active disease, or at least 6 months of follow-up for preventing relapse in quiescent disease were analyzed. We included any antibiotics alone or in combination using predefined definitions of remission and relapse. Two reviewers independently assessed eligibility and extracted data. The primary outcome was remission or relapse using an intention-to-treat methodology. The data were summarized using relative risk (RR) and pooled using a random effects model. For active CD, there were 10 RCTs involving 1,160 patients. There was a statistically significant effect of antibiotics being superior to placebo (RR of active CD not in remission=0.85; 95% confidence interval (CI)=0.73-0.99, P=0.03). There was moderate heterogeneity between results (I(2)=48%) and a diverse number of antibiotics were tested (anti-tuberculosis therapy, macrolides, fluroquinolones, 5-nitroimidazoles, and rifaximin) either alone or in combination. Rifamycin derivatives either alone or in combination with other antibiotics appeared to have a significant effect at inducing remission in active CD. In perianal CD fistula there were three trials evaluating 123 patients using either ciprofloxacin or metronidazole. There was a statistically significant effect in reducing fistula drainage (RR=0.8; 95% CI=0.66-0.98) with no heterogeneity (I(2)=0%) and an number needed to treat 5 (95% CI=3-20). For quiescent CD, there were 3 RCTs involving 186 patients treated with different antibiotics combinations (all including antimycobacterials) vs. placebo. There was a statistically significant effect in favor of antibiotics vs. placebo (RR of relapse=0.62; 95% CI=0.46-0.84), with no heterogeneity (I(2)=0%). In active UC, there were 9 RCTs with 662 patients and there was a statistically significant benefit for antibiotics inducing remission (RR of UC not in remission=0.64; 95% CI=0.43-0.96). There was moderate heterogeneity (I(2)=69%) and antibiotics used were all different single or combination drugs. Antibiotic therapy may induce remission in active CD and UC, although the diverse number of antibiotics tested means the data are difficult to interpret. This systematic review is a mandate for further trials of antibiotic therapy in IBD.
Asunto(s)
Antibacterianos/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Colitis Ulcerosa/fisiopatología , Enfermedad de Crohn/fisiopatología , Combinación de Medicamentos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Inducción de Remisión/métodos , Rifamicinas/uso terapéutico , Riesgo , Prevención Secundaria , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Adherence to medication in inflammatory bowel disease (IBD) improves outcomes. Current practices of screening for adherence to IBD medications are unknown. The goal of this study was to determine current practice and perception of screening for medication adherence among US-based gastroenterologists. METHODS: A survey was mailed electronically to gastroenterologists whose electronic-mail address was listed in the American College of Gastroenterology database. Physicians who cared for IBD patients were invited to answer. RESULTS: About 6830 surveys were sent to gastroenterologists nationwide, and 395 physicians who cared for IBD patients completed the survey. The true response rate is unknown, as the number of physicians caring for IBD patients in the database is unknown. About 77% (n = 303) of physicians who responded stated they screen for adherence to medication. Of the 77% of physicians who screened for adherence, only 19% (n = 58) use accepted measures of screening for adherence (pill counts, prescription refill rates, or adherence surveys). The remaining 81% used patient interview to screen for adherence, a measure considered least accepted to determine adherence, as it overestimates adherence. The average number of IBD patients observed in 1 week had no statistical significance in predilection for screening (P = 0.82). Private practice physicians (P = 0.05), younger physicians (P = 0.03), and physicians with fewer years of experience (P = 0.02) all were more likely to screen. About 95% of responders thought determining a low adherer to medicine was important because an intervention can increase adherence. CONCLUSIONS: The majority of gastroenterologists surveyed recognize that adherence to medication is important and improves outcomes. The majority of physicians in this study are screening for nonadherence in IBD, but are not using accepted measures for adherence detection. If this study truly reflects the majority of physicians nationwide, changing the way physicians screen for adherence, may detect more low adherers to medication.
Asunto(s)
Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Actitud del Personal de Salud , Femenino , Gastroenterología/métodos , Gastroenterología/estadística & datos numéricos , Encuestas de Atención de la Salud , Humanos , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina/normas , Práctica Profesional/estadística & datos numéricos , Estados UnidosRESUMEN
Longstanding and extensive ulcerative colitis (UC) are associated with the subsequent development of colorectal cancer (CRC). This article summarizes key strategies for colonoscopic surveillance, the most widely used and evidence-based method of CRC prevention. As currently constituted and practiced, surveillance examinations every 1 to 3 years with lesion detection and removal using high-definition endoscopic systems with or without pancolonic spray-dye chromoendoscopy is the best method for mitigating the development of CRC morbidity and mortality. For patients with primary sclerosing cholangitis with UC, surveillance should begin at the time of diagnosis and colonoscopy should be performed annually.
Asunto(s)
Colitis Ulcerosa/complicaciones , Colonoscopía/métodos , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/prevención & control , Vigilancia de la Población/métodos , Colangitis Esclerosante/complicaciones , Colitis Ulcerosa/patología , Humanos , RiesgoRESUMEN
PURPOSE: We evaluated a large cohort of patients with longstanding ulcerative colitis in a colonoscopic surveillance program to determine predictors of colectomy. METHODS: We queried a retrospective database of patients who had symptoms of ulcerative colitis for seven years or more. Histologic inflammation in biopsies was graded on a validated four-point scale: absent, mild, moderate, severe. We performed a multivariate analysis of the inflammation scores and other variables to determine predictive factors for colectomy. Patients who underwent colectomy for neoplasia were censored at the time of surgery; those who did not undergo colectomy were censored at the time of last contact. RESULTS: A total of 561 patients were evaluated, with a median follow-up of 21.4 years since disease onset. A total of 97 patients (17.3 percent) underwent surgery; 25 (4.5 percent) for reasons other than dysplasia. These 25 constitute events for this analysis. For univariate analysis, mean inflammation (P < 0.001) and steroid use (P = 0.01) were predictors of colectomy. For multivariable proportional hazards analysis, mean inflammation (P < 0.001) and steroid use (P = 0.03) were predictors of colectomy, whereas salicylate use (P = 0.007) was protective. CONCLUSIONS: Higher median inflammation scores and corticosteroid use were predictors of colectomy in this patient population. The overall rate of colectomy during a long period of follow-up was low (<1 percent per year).