Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn's Disease Patients on Ustekinumab.

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index ≤ 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission.

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn's Disease Patients: The SUSTAIN Study.

BACKGROUND: Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn's disease (CD) patients in real-world clinical practice. METHODS: A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. RESULTS: A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). CONCLUSIONS: Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice.

This large retrospective study demonstrated the short- and long-term effectiveness and safety of ustekinumab in patients with Crohn's disease in real-world clinical practice, including those with refractory disease.

Factores pronósticos de mortalidad en la cirrosis hepática tras un primer episodio de peritonitis bacteriana espontánea. Estudio multicéntrico / Prognostic factors of liver cirrhosis mortality after a first episode of spontaneous bacterial peritonitis. A multicenter study

Introducción: la peritonitis bacteriana espontánea es una complicación infecciosa con impacto negativo sobre la supervivencia de los pacientes con cirrosis. Objetivo: analizar la supervivencia a corto y largo plazo después de un primer episodio de peritonitis bacteriana espontánea y los factores pronósticos asociados. Material y métodos: estudio multicéntrico retrospectivo que incluyó a los pacientes ingresados por peritonitis bacteriana espontánea entre 2008 y 2013. Las variables independientes relacionadas con la mortalidad se analizaron mediante regresión logística. Se analizó el poder pronóstico de los índices Child Pugh, MELD y Charlson mediante curva de ROC. Resultados: fueron incluidos 159 pacientes. El 72% fueron hombres con una edad media de 63,5 años y con una puntuación MELD de 19 (DE ± 9,5). La mortalidad a los 30 días, 90 días, al año y a los dos años fue del 21%, 31%, 55% y 69%, respectivamente. La encefalopatía hepática (p = 0,008; OR 3,5; IC 95% 1,4-8,8) y la función renal (p = 0,026; OR 2,7; IC 95% 1,13-16,7) fueron factores independientes de mortalidad a corto y largo plazo. El MELD fue un buen indicador de supervivencia a corto y largo plazo (área bajo la curva [AUC] 0,7: IC 95% 1,02-1,4). El índice de Charlson se relacionó con la mortalidad a largo plazo (AUC 0,68: IC 95% 0,6-0,77). Conclusiones: en la peritonitis bacteriana espontánea la mortalidad a corto y largo plazo sigue siendo elevada. Los principales factores pronósticos de mortalidad son el deterioro de la función hepática y renal. El MELD y el índice de Charlson son unos buenos indicadores de supervivencia (AU)

Introduction: Spontaneous bacterial peritonitis is an infectious complication with a negative impact on survival of patients with cirrhosis. Objective: To analyze the short- and long-term survival after a first episode of bacterial peritonitis and the associated prognostic factors. Patients and methods: This was a retrospective, multicenter study of patients admitted to hospital for spontaneous bacterial peritonitis between 2008 and 2013. Independent variables related to mortality were analyzed by logistic regression. The prognostic power of the Child Pugh Score, the Model for End-Stage Liver Disease (MELD) and the Charlson index was analyzed by ROC curve. Results: A total of 159 patients were enrolled, 72% were males with a mean age of 63.5 years and a mean MELD score of 19 (SD ± 9.5). Mortality at 30 and 90 days and one and two years was 21%, 31%, 55% and 69%, respectively. Hepatic encephalopathy (p = 0.008, OR 3.5, 95% CI 1.4-8.8) and kidney function (p = 0.026, OR 2.7, 95% CI 1.13-16.7) were independent factors for short- and long-term mortality. MELD was a good marker of short- and long-term survival (area under the curve [AUC] 0.7: 95% CI 1.02-1.4). The Charlson index was related to long-term mortality (AUC 0.68: 95% CI 0.6-0.77). Conclusions: Short- and long-term mortality of spontaneous bacterial peritonitis is still high. The main prognostic factors for mortality are impairment of liver and kidney function. MELD and the Charlson index are good markers of survival (AU)

Prognostic factors of liver cirrhosis mortality after a first episode of spontaneous bacterial peritonitis. A multicenter study.

INTRODUCTION: Spontaneous bacterial peritonitis is an infectious complication with a negative impact on survival of patients with cirrhosis. OBJECTIVE: To analyze the short- and long-term survival after a first episode of bacterial peritonitis and the associated prognostic factors. PATIENTS AND METHODS: This was a retrospective, multicenter study of patients admitted to hospital for spontaneous bacterial peritonitis between 2008 and 2013. Independent variables related to mortality were analyzed by logistic regression. The prognostic power of the Child Pugh Score, the Model for End-Stage Liver Disease (MELD) and the Charlson index was analyzed by ROC curve. RESULTS: A total of 159 patients were enrolled, 72% were males with a mean age of 63.5 years and a mean MELD score of 19 (SD ± 9.5). Mortality at 30 and 90 days and one and two years was 21%, 31%, 55% and 69%, respectively. Hepatic encephalopathy (p = 0.008, OR 3.5, 95% CI 1.4-8.8) and kidney function (p = 0.026, OR 2.7, 95% CI 1.13-16.7) were independent factors for short- and long-term mortality. MELD was a good marker of short- and long-term survival (area under the curve [AUC] 0.7: 95% CI 1.02-1.4). The Charlson index was related to long-term mortality (AUC 0.68: 95% CI 0.6-0.77). CONCLUSIONS: Short- and long-term mortality of spontaneous bacterial peritonitis is still high. The main prognostic factors for mortality are impairment of liver and kidney function. MELD and the Charlson index are good markers of survival.

Asistencia urgente a los pacientes con hemorragia digestiva alta en los hospitales comarcales catalanes / Emergency care of patients with upper gastrointestinal bleeding in regional hospitals in Catalonia

Objetivo Valorar los recursos disponibles en los hospitales comarcales catalanes para la asistencia urgente de la hemorragia digestiva alta. Método Se analiza una encuesta enviada a 32 hospitales, sobre la existencia, composición y recursos del turno de guardia (TDG) de endoscopia, referida al año 2009.ResultadosRespondieron 24 centros, que cubrían la asistencia de 3.954.000 habitantes. Tenían TDG 12 hospitales. No disponían de TDG en su centro de referencia 1.483.000 habitantes. Los centros con TDG tenían más camas y cubrían más población. Los TDG estaban formados por 4,5 endoscopistas (rango 2-11), que cubrían 82,1 (33,2-182,5) guardias/año. Diecisiete centros reportaban 1.571 episodios (51 por centro, rango 3-280, 39,68/100.000 hab.). Los centros con TDG reportaban más casos (76 vs. 43, p=0,047). Los que no disponen de TDG derivaron más pacientes (147 vs. 17, p= 0,001). Los pacientes en urgencias estaban a cargo de medicina interna en 4 centros, de cirugía en 14 y repartidos entre ambos servicios en 6. Si ingresaban, quedaron a cargo de Digestivo solo en 6 hospitales. Los recursos más utilizados eran la ligadura en la hemorragia varicosa y las terapias de inyección en la no varicosa. Un 21% de centros no realizaban tratamiento combinado. Conclusiones Una proporción significativa de la población no dispone de endoscopista de guardia en su centro de referencia. La constitución de TDG en hospitales comarcales supone importantes cargas asistenciales. La coordinación entre profesionales y centros permitiría la aplicación eficiente de los recursos terapéuticos y el establecimiento de TDG en centros que no tienen (AU)

Objective To evaluate the resources available in Catalan regional hospitals for the emergency care of upper gastrointestinal hemorrhage. Methods We analyzed a survey sent to 32 hospitals on the availability, composition and resources of a duty endoscopy service for the year 2009.ResultsResponses were obtained from 24 centers, covering 3,954,000 inhabitants. Duty endoscopists were available in 12 hospitals. A total of 1,483,000 inhabitants were unable to access a duty endoscopist in the referral center. Centers with duty endoscopists had more beds and had a larger catchment area. Duty services were composed of 4.5 endoscopists (range 2-11), covering 82.1 (33.2-182.5) duty shifts/year. Seventeen centers reported 1,571 episodes (51%, range: 3-280, 39.68/100,000 inhabitants). Centers with a duty service reported a greater number of cases (76 vs. 43, p=0.047). Centers without this service referred a greater number of patients (147 vs. 17, p=0.001). Patients in the emergency department were under the care of the internal medicine department in four centers, the surgery department in 14 centers and under the care of both departments in six. Admitted patients were under the care of the gastroenterology department in only six hospitals. The most widely used procedures were ligation of varicose bleeding and injection therapies in non-varicose bleeding. Twenty-one percent of centers did not perform combined treatment. Conclusions A significant proportion of the population does not have access to a duty endoscopist in referral centers. Duty shifts represent significant workload in regional hospitals. Coordination among health professionals and centers would allow the efficient application of therapeutic resources and a duty endoscopy service to be established in centers lacking this resource (AU)