Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Search for standard model production of four top quarks in the lepton + jets channel in pp collisions at √s = 8 TeV

Open Access, Copyright CERN, for the benefit of the CMS Collaboration. Article funded by SCOAP3.Abstract: A search is presented for standard model (SM) production of four top quarks (Formula presented.) in pp collisions in the lepton + jets channel. The data correspond to an integrated luminosity of 19.6 fb−1 recorded at a centre-of-mass energy of 8 TeV with the CMS detector at the CERN LHC. The expected cross section for SM (Formula presented.) production is (Formula presented.). A combination of kinematic reconstruction and multivariate techniques is used to distinguish between the small signal and large background. The data are consistent with expectations of the SM, and an upper limit of 32 fb is set at a 95% confidence level on the cross section for producing four top quarks in the SM, where a limit of 32 ± 17 fb is expected

Beneficios del tratamiento erradicador de la infección por Helicobacter pylori en pacientes ulcerosos en un centro de atención primaria

ObjetivoEvaluar la evolución clínica y la utilización de recursos sanitarios en atención primaria un año después del tratamiento erradicador de Helicobacter pylori (Hp) en pacientes con úlcera péptica e infección por Hp.DiseñoEstudio retrospectivo sobre el efecto de una intervención.Ámbito del estudioCentro de atención primaria urbano y reformado.PacientesCiento dos pacientes con enfermedad ulcerosa péptica e infección por Hp.IntervenciónTratamiento erradicador de Hp.Mediciones y resultados principalesa) número de visitas totales (VT); b) visitas por dispepsia (VD); c) número de brotes ulcerosos (BU), y d) fármacos consumidos para tratamiento de la dispepsia. De los pacientes tratados un 79,4% era varón. La edad media global fue de 47,8 ± 12,4 años. Después de la intervención, disminuyeron significativamente las VT (de 8,3 a 6,6; p < 0,001), las VD (3,1 a 1,1; p < 0,00001), y los BU (de 1,2 a 0,06; p < 0,00001). El número medio de fármacos prescritos para la dispepsia por paciente disminuyó de 1,24 a 0,43 (p < 0,0001). La prescripción de ranitidina pasó de 72,7 a 13,8 días (p < 0,001) y la de omeprazol disminuyó de 35,1 a 12,2 días (p < 0,03). El ahorro total estimado por paciente fue de 26.792 pts. con valores económicos de 1998.ConclusionesEn nuestro medio el tratamiento erradicador en pacientes ulcerosos Hp (+) disminuye las necesidades de asistencia y la prescripción de medicamentos antiulcerosos. Ya durante el primer año esto supone un beneficio clínico para estos pacientes y un ahorro económico importante para la sanidad pública.ObjectivesTo evaluate the clinical evolution and the use of Primary Care health resources one year after treatment to eradicate Helicobacter pylori (Hp) infection in patients with peptic ulcers and Hp infection.DesignRetrospective study on the effect of an intervention.SettingUrban, reformed primary care centre.Patients102 patients with peptic ulcers and Hp infection.InterventionTreatment to eradicate Hp.Measurements and main resultsa) Total medical attendance; b) attendance for dyspepsia; c) number of ulcerous outbreaks; d) medicines taken to treat dyspepsia. 79.4% of the patients treated were male. Overall mean age was 47.8 ± 12.4. After the intervention, total attendance (from 8.3 to 6.6, p < 0.001), attendance for dyspepsia (from 3.1 to 1.1, p < 0.00001), and ulcerous outbreaks (from 1.2 to 0.06, p < 0.00001) all dropped sharply. The mean number of medicines prescribed for dyspepsia per patient fell from 1.24 to 0.43, p < 0.0001. Ranitidine prescription fell from 72.7 to 13.8 days (p < 0.001); and omeprazol from 35.1 to 12.2 days (p < 0.03). Estimated total saving per patient was 26792 pesetas at 1998 values.ConclusionsTreatment in primary care to eradicate Hp (+) in ulcerous patients reduced the needs of attendance and the prescription of drugs for ulcers. Just in the first year this supposed a clinical benefit for these patients and important economic savings for the public health service

Patients&#39; perceptions of the impact of ulcerative colitis on social and professional life: results from the UC-LIFE survey of outpatient clinics in Spain

Xavier Calvet,1&ndash;3 Federico Arg&uuml;elles-Arias,4 Antonio L&oacute;pez-Sanrom&aacute;n,5 Luis Cea-Calvo,6 Berta Juli&aacute;,6 Cristina Romero de Santos,6 Daniel Carpio7 1Hospital de Sabadell. Corporaci&oacute; Sanit&agrave;ria Universit&agrave;ria Parc Taul&iacute;, Sabadell, Spain; 2Centro de investigaci&oacute;n biom&eacute;dica en red de enfermedades hep&aacute;ticas y digestivas (CIBEREHD), Spain; 3Department of Medicine, Universitat Aut&ograve;noma de Barcelona, Bellaterra, Spain; 4UGC Digestivo Intercentros Hospitales Virgen Macarena-Roc&iacute;o, Seville, Spain; 5Section of Gastroenterology, Department of Gastroenterology and Hepatology, Hospital Ram&oacute;n y Cajal, Madrid, Spain; 6Medical Affairs Department, Merck Sharp &amp; Dohme, Madrid, Spain; 7Service of Gastroenterology Complexo Hospitalario Universitario de Pontevedra, Instituto de Investigaci&oacute;n Biomedica (IBI), Pontevedra, Spain Purpose: Ulcerative colitis (UC) may cause many patients to miss out on important personal and professional opportunities. We therefore conducted a survey (UC-LIFE) to assess patients&rsquo; perceptions of the impact of UC on social and professional lives. Patients and methods: Consecutive unselected UC patients aged &ge;18 years were recruited from 38 outpatient clinics in Spain. Patients completed the survey at home, returning it by post. The survey comprised 44 multiple-choice questions, including questions about the impact of UC on social, personal, professional, and academic activities. Results: Of 585 patients invited, 436 (75%) returned the survey (mean age 46 years; 47% women). High proportions of patients considered their disease &ldquo;sometimes&rdquo;, &ldquo;frequently&rdquo; or &ldquo;mostly/always&rdquo; influenced leisure activities (65.1%), recreational or professional activities (57.6%), or relationships with relatives or friends (9.9%). Patients also reported that UC influenced their decision to have children (17.2%), or their ability to take care of children (40.7%); these percentages were higher in women and in younger patients. Overall, 47.0% of patients declared that UC influenced the kind of job they performed, 20.3% had rejected a job due to UC, 14.7% had lost a job due to UC, and 19.4% had had academic problems due to UC. Conclusion: Beyond symptoms alone, UC imposes an enormous additional burden on patients&rsquo; social, professional, and family lives. This extra burden clearly needs to be addressed so that the ultimate goal of IBD treatment &ndash; normalization of patient quality of life &ndash; can be attained by as many patients as possible. Keywords: disease burden, patient-reported outcomes, patients&rsquo; perceptions, quality of life, ulcerative coliti

Tuberculosis in Anti-Tumour Necrosis Factor-treated Inflammatory Bowel Disease Patients After the Implementation of Preventive Measures: Compliance With Recommendations and Safety of Retreatment.

Despite having adopted preventive measures, tuberculosis (TB) may still occur in patients with inflammatory bowel disease (IBD) treated with anti-tumour necrosis factor (anti-TNF). Data on the causes and characteristics of TB cases in this scenario are lacking. Our aim was to describe the characteristics of TB in anti-TNF-treated IBD patients after the publication of the Spanish TB prevention guidelines in IBD patients and to evaluate the safety of restarting anti-TNF after a TB diagnosis. In this multicentre, retrospective, descriptive study, TB cases from Spanish hospitals were collected. Continuous variables were reported as mean and standard deviation or median and interquartile range. Categorical variables were described as absolute and relative frequencies and their confidence intervals when necessary. We collected 50 TB cases in anti-TNF-treated IBD patients, 60% male, median age 37.3 years (interquartile range [IQR] 30.4-47). Median latency between anti-TNF initiation and first TB symptoms was 155.5 days (IQR 88-301); 34% of TB cases were disseminated and 26% extrapulmonary. In 30 patients (60%), TB cases developed despite compliance with recommended preventive measures; *not performing 2-step TST (tuberculin skin test) was the main failure in compliance with recommendations. In 17 patients (34%) anti-TNF was restarted after a median of 13 months (IQR 7.1-17.3) and there were no cases of TB reactivation. Tuberculosis could still occur in anti-TNF-treated IBD patients despite compliance with recommended preventive measures. A significant number of cases developed when these recommendations were not followed. Restarting anti-TNF treatment in these patients seems to be safe

Ustekinumab versus adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn's disease: a multicentre, randomised, double-blind, parallel-group, phase 3b trial

Background: Active-comparator trials are important to inform patient and physician choice. We aimed to evaluate the efficacy and safety of monotherapy with either ustekinumab or adalimumab in biologic-naive patients with moderately to severely active Crohn's disease. Methods: We conducted a randomised, double-blind, parallel-group, active-comparator, phase 3b trial (SEAVUE) at 121 hospitals or private practices in 18 countries. We included biologic-naive patients aged 18 years or older with moderately to severely active Crohn's disease and a Crohn's Disease Activity Index (CDAI) score of 220–450, who had not responded to or were intolerant to conventional therapy (or were corticosteroid dependent) and had at least one ulcer of any size at baseline endoscopic evaluation. Eligible patients were randomly assigned (1:1; via an interactive web response system) to receive ustekinumab (approximately 6 mg/kg intravenously on day 0, then 90 mg subcutaneously once every 8 weeks) or adalimumab (160 mg on day 0, 80 mg at 2 weeks, then 40 mg once every 2 weeks, subcutaneously) through week 56. Study treatments were administered as monotherapy and without dose modifications. Patients, investigators, and study site personnel were masked to treatment group assignment. The primary endpoint was the proportion of patients who were in clinical remission (CDAI score <150) at week 52 in the intention-to-treat population (ie, all patients who were randomly assigned to a treatment group). This trial is registered with ClinicalTrials.gov, NCT03464136, and EudraCT, 2017-004209-41. Findings: Between June 28, 2018, and Dec 12, 2019, 633 patients were assessed for eligibility and 386 were enrolled and randomly assigned to receive ustekinumab (n=191) or adalimumab (n=195). 29 (15%) of 191 patients in the ustekinumab group and 46 (24%) of 195 in the adalimumab group discontinued study treatment before week 52. There was no significant difference between the ustekinumab and adalimumab groups in the occurrence of the primary endpoint; at week 52, 124 (65%) of 191 patients in the ustekinumab group versus 119 (61%) of 195 in the adalimumab group were in clinical remission (between-group difference 4%, 95% CI –6 to 14; p=0·42). Safety for both groups was consistent with previous reports. Serious infections were reported in four (2%) of 191 patients in the ustekinumab group and five (3%) of 195 in the adalimumab group. No deaths occurred through week 52 of the study. Interpretation: Both ustekinumab and adalimumab monotherapies were highly effective in this population of biologic-naive patients, with no difference in the primary outcome between the drugs. Funding: Janssen Scientific Affairs