Activity of Spanish gastroenterology units before and after the COVID-19 pandemic: an assessment using the EFIC_AD tool, developed by the Sociedad Española de Patología Digestiva (SEPD).

INTRODUCTION: the COVID-19 pandemic had a strong impact on the healthcare model. The Sociedad Española de Patología Digestiva (SEPD) offered gastroenterology care units (UAAD) an instrument (EFIC_AD) to record and analyze their efficacy and efficiency. Thus, the impact of the pandemic on the activity of UAAD was assessed. METHODS: A descriptive study, based on the EFIC_AD registry for the period 2019-2021, of activity regarding admissions, clinic visits, and endoscopic as well as non-endoscopic tests, and endoscopy room performance. RESULTS: data were collected from up to 42 hospitals (22 with ≥ 500 beds). Overall, activity during 2020 compared to 2019 decreased by 12.30 % for admissions and 40 % for pH-metries (16.70 % for new clinic visits; 14.34 % for referrals from primary care; 24.70 % for gastroscopies; 32.50 % for colonoscopies; 31.00 % for endoscopic ultrasounds; 18.20 % for endoscopic retrograde cholangiopancreatography (ERCPs); 38.00 % for manometries; 23.60 % for abdominal ultrasounds; 36.17 % for liver transient elastographies [Fibroscan®]). The levels achieved during 2019 were not fully recovered during 2021 except for digestive motility studies, and virtually for endoscopy room performance rate (88.15 % in 2019; 67.77 % in 2020; 85.93 % in 2021). CONCLUSIONS: during 2020 the COVID-19 pandemic led to a markedly decreased in specific activities at UAAD, which was not fully recovered in 2021 despite endoscopy room performance return to normal.

Rapidity of clinical response to adalimumab and improvement of quality of life in luminal Crohn's disease: RAPIDA study.

OBJECTIVE: No studies evaluating the rapidity of response to biological therapies are available for Crohn's disease (CD). The aim of this study was to evaluate rapidity of onset of clinical response and impact on quality of life (QoL) of adalimumab therapy in adult anti-TNF-naïve patients with moderately-to-severely active CD. PATIENTS AND METHODS: RAPIDA was an open-label, single-arm, prospective, multicenter clinical trial. Adult patients with moderately-to-severely active luminal CD, anti-TNF-naïve, and unresponsive to conventional therapy were treated with adalimumab. Clinical disease activity, QoL and inflammatory biomarkers were measured at day 4, and weeks 1, 2, 4, and 12 after treatment initiation. RESULTS: Eighty-six patients were included in the intention-to-treat (ITT) analyses. Clinical disease activity was reduced from a median of 9.0 points to 6.0 points at day 4. Clinical response (≥ 3-point reduction in the Harvey-Bradshaw Index, HBI) was achieved by 61.6% (d4) and 75.6% (w1) of patients in the ITT population (median 2.5 days) and with non-responder imputation (NRI), by 55.8% and 53.4%, respectively. The proportion of patients in clinical remission (HBI<5) at weeks 2 and 4 in the ITT population was 54.7% and 62.8%, respectively (median 7.0 days), and 38.4% and 45.3% in the NRI population. All QoL scores significantly improved and inflammatory biomarkers significantly decreased from day 4 onwards (p<0.0001). CONCLUSION: Rapid clinical response and remission, improvement in QoL and fatigue, and a reduction of inflammatory biomarkers were achieved with adalimumab as early as day 4 in adult anti-TNF-naïve patients with moderately-to-severely active CD.

The Harvey-Bradshaw Index Adapted to a Mobile Application Compared with In-Clinic Assessment: The MediCrohn Study.

Objectives: Mobile apps are useful tools in e-health and self-management strategies in disease monitoring. We evaluated the Harvey-Bradshaw index (HBI) mobile app self-administered by the patient to see if its results agreed with HBI in-clinic assessed by a physician. Methods: Patients were enrolled in a 4-month prospective study with clinical assessments at months 1 and 4. Patients completed mobile app HBI and within 48 h, HBI was performed by a physician (gold standard). HBI scores characterized Crohn's disease (CD) as remission <5 or active ≥5. We determined agreement per item and total HBI score and intraclass correlation coefficients (ICCs). Bland-Altman plot was performed. HBI changes in disease activity from month 1 to month 4 were determined. Results: A total of 219 patients were enrolled. All scheduled assessments (385 pairs of the HBI questionnaire) showed a high percentage of agreement for remission/activity (92.4%, κ = 0.796), positive predictive value (PPV) for remission of 98.2%, and negative predictive value of 76.7%. High agreement was also found at month 1 (93.15%, κ = 0.82) and month 4 (91.5%, κ = 0.75). Bland-Altman plot was more uniform when the HBI mean values were <5 (remission). ICC values were 0.82, 0.897, and 0.879 in all scheduled assessments, 1 and 4 months, respectively. Conclusions: We found a high percentage of agreement between patients' self-administered mobile app HBI and in-clinic physician assessment to detect CD activity with a remarkably high PPV for remission. The mobile app HBI might allow a strict control of inflammation by remote monitoring and flexible follow-up of CD patients. Reduction of sanitary costs could be possible.

Predictive factors of clinical response to treatment with anti-TNF agents in ulcerative colitis: what have we learned from our patients?

INTRODUCTION: inhibitors of tumor necrosis factor alpha (anti-TNFs) are effective drugs for the treatment of moderate-to-severe ulcerative colitis (UC). However, many patients do not respond or lose therapeutic response during follow-up. OBJECTIVES: to analyze the determining factors of clinical response to anti-TNFs in UC. METHODS: a multicenter retrospective study was performed in 79 patients with UC who started treatment with anti-TNFs between 2009 and 2015. The primary endpoint was clinical remission (pMayo index ≤ 1) at 12 months. Furthermore, remission and clinical response (final pMayo score ≤ 3) and corticoids discontinuation were assessed at three, six and 12 months. An analysis was performed to identify variables predictive of clinical response. RESULTS: at 12 months, remission and clinical response were seen in 59.2 % and 77.8 % of patients, respectively. Corticoids could be discontinued in 82.4 % of patients. At 12 months, corticoids discontinuation (< 3 months) (OR 0.06; 95 % CI: 0.01-0.24) and clinical response at six months (OR 0.008; 95 % CI: 0.001-0.053) were independent factors predictive of clinical remission. CONCLUSION: in patients with active UC on anti-TNFs, corticoid discontinuation within three months and clinical response at six months after treatment onset are predictive of clinical disease remission.

Eikenella corrodens lipopolysaccharide stimulates the pro-atherosclerotic response in human coronary artery endothelial cells and monocyte adhesion.

Eikenella corrodens is a gram-negative bacterium, and although primarily associated with periodontal infections or infective endocarditis, it has been identified in coronary atheromatous plaques. The effect of its lipopolysaccharide (LPS) on human coronary artery endothelial cells (HCAECs) is unknown. Our aim was to examine the mechanism underlying the inflammatory response in HCAECs stimulated with E. corrodens-LPS and to evaluate monocyte adhesion. Endothelial responses were determined by measuring the levels of chemokines and cytokines using flow cytometry. The surface expression of intercellular adhesion molecule 1 (ICAM-1) was determined using a cell-based ELISA, and the adhesion of THP-1 monocytes to HCAECs was also monitored. The involvement of toll-like receptors (TLRs) 2 and 4 was examined using TLR-neutralizing antibodies, and activation of extracellular signal-regulated kinase (ERK)1/2 and nuclear factor-kappa B (NF-κB) p65 were measured by western blotting and ELISA, respectively. Eikenella corrodens-LPS increased secretion of interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and granulocyte-macrophage colony-stimulating factor (GM-CSF), and expression of ICAM-1 on the surface of HCAECs, consistent with the increased adhesion of THP-1 cells. Moreover, E. corrodens-LPS interacted with TLR4, a key receptor able to maintain the levels of IL-8, MCP-1, and GM-CSF in HCAECs. Phosphorylation of ERK1/2 and activation of NF-κB p65 were also increased. The results indicate that E. corrodens-LPS activates HCAECs through TLR4, ERK, and NF-κB p65, triggering a pro-atherosclerotic endothelial response and enhancing monocyte adhesion.

Clinical status, quality of life, and work productivity in Crohn's disease patients after one year of treatment with adalimumab.

OBJECTIVE: Clinical trials have shown the efficacy of adalimumab in Crohn's disease, but the outcome in regular practice remains unknown. The aim of the study was to examine clinical status, quality of life, and work productivity of Crohn's disease patients receiving adalimumab for one year in the context of usual clinical practice. MATERIAL AND METHODS: This was a prospective, observational study with a one-year follow-up. After baseline, Crohn's disease patients were evaluated at 1, 3, 6, 9, and 12 months after starting treatment with adalimumab. Outcome variables included: clinical status (measured with CDAI), quality of life (measured with EuroQoL-5D and IBDQ), and work productivity (measured with WPAI questionnaire). These outcome variables were compared using the Student's t test or Wilcoxon test for paired comparison data according to the data distribution. Statistical significance was set at two-sided p < 0.05. RESULTS: The sample was composed of 126 patients (age [mean] 39.1 ± [standard deviation] 13.8 years; 51% male). Significant changes were observed during the follow-up period: CDAI decreased from [median] 194 ([25-75 percentiles] 121-269) to 48.2 (10.1-122.0) (p < 0.05); the EuroQoL-5D increased from 0.735 (0.633-0.790) to 0.797 (0.726-1.000) (p < 0.05); the EuroQoL-5D visual analogue scale increased from 50.0 (40-70) to 80.0 (60-90); (p < 0.05) and the IBDQ increased from 56.7 (51.6-61.5) to 67.5 (60.1-73.6) (p < 0.05). The total work productivity impact decreased from 53% to 24% (p < 0.05). CONCLUSIONS: In regular practice, adalimumab is clinically effective in the treatment of Crohn's disease patients and results in a significant improvement in quality of life and work productivity.

Controversies in the management of anti-TNF therapy in patients with Crohn's disease: a Delphi consensus.

BACKGROUND: Despite research, there are still controversial areas in the management of Crohn's disease (CD). OBJECTIVE: To establish practical recommendations on using anti-tumour necrosis factor (TNF) drugs in patients with moderate-to-severe CD. METHODS: Clinical controversies in the management of CD using anti-TNF therapies were identified. A comprehensive literature review was performed, and a national survey was launched to examine current clinical practices when using anti-TNF therapies. Their results were discussed by expert gastroenterologists within a nominal group meeting, and a set of statements was proposed and tested in a Delphi process. RESULTS: Qualitative study. The survey and Delphi process were sent to 244 CD-treating physicians (response rate: 58%). A total of 14 statements were generated. All but two achieved agreement. These statements cover: (1) use of first-line non-anti-TNF biological therapy; (2) role of HLA-DQA1*05 in daily practice; (3) attitudes in primary non-response and loss of response to anti-TNF therapy due to immunogenicity; (4) use of ustekinumab or vedolizumab if a change in action mechanism is warranted; (5) anti-TNF drug level monitoring; (6) combined therapy with an immunomodulator. CONCLUSION: This document sought to pull together the best evidence, experts' opinions, and treating physicians' attitudes when using anti-TNF therapies in patients with CD.

Serum and Urine Metabolomic Profiling of Newly Diagnosed Treatment-Naïve Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a prevalent chronic noncurable disease associated with profound metabolic changes. The discovery of novel molecular indicators for unraveling IBD etiopathogenesis and the diagnosis and prognosis of IBD is therefore pivotal. We sought to determine the distinctive metabolic signatures from the different IBD subgroups before treatment initiation. METHODS: Serum and urine samples from newly diagnosed treatment-naïve IBD patients and age and sex-matched healthy control (HC) individuals were investigated using proton nuclear magnetic resonance spectroscopy. Metabolic differences were identified based on univariate and multivariate statistical analyses. RESULTS: A total of 137 Crohn's disease patients, 202 ulcerative colitis patients, and 338 HC individuals were included. In the IBD cohort, several distinguishable metabolites were detected within each subgroup comparison. Most of the differences revealed alterations in energy and amino acid metabolism in IBD patients, with an increased demand of the body for energy mainly through the ketone bodies. As compared with HC individuals, differences in metabolites were more marked and numerous in Crohn's disease than in ulcerative colitis patients, and in serum than in urine. In addition, clustering analysis revealed 3 distinct patient profiles with notable differences among them based on the analysis of their clinical, anthropometric, and metabolomic variables. However, relevant phenotypical differences were not found among these 3 clusters. CONCLUSIONS: This study highlights the molecular alterations present within the different subgroups of newly diagnosed treatment-naïve IBD patients. The metabolomic profile of these patients may provide further understanding of pathogenic mechanisms of IBD subgroups. Serum metabotype seemed to be especially sensitive to the onset of IBD.

Persistence, effectiveness and safety of ustekinumab and vedolizumab therapy for complex perianal fistula in Crohn's disease: The HEAL study from GETECCU.

BACKGROUND: The efficacy of ustekinumab and vedolizumab for treating complex perianal fistula in Crohn's disease has been barely studied. We aimed to assess treatment persistence, clinical remission, and safety of these drugs in this context. METHODS: Crohn's disease patients who had received ustekinumab or vedolizumab for the indication of active complex perianal fistula, were included. Clinical remission was defined according to Fistula Drainage Assessment Index (no drainage through the fistula upon gentle pressure) based on physicians' assessment. RESULTS: Of 155 patients, 136 received ustekinumab, and 35 vedolizumab (16 received both). Median follow-up for ustekinumab was 27 months. Among those on ustekinumab, 54 % achieved remission, and within this group, 27 % relapsed during follow-up. The incidence rate of relapse was 11 % per patient-year. Multivariate analysis found no variables associated with treatment discontinuation or relapse. Median follow-up time for patients receiving vedolizumab was 19 months. Remission was achieved in 46 % of the patients receiving vedolizumab, and among them, 20 % relapsed during follow-up. The incidence rate of relapse was 7 % per patient-year. Adverse events were mild in 6 % on ustekinumab and 8 % on vedolizumab. CONCLUSION: Ustekinumab and vedolizumab appear effective, achieving remission in around half of complex perianal fistula patients, with favorable safety profiles.

Predictors: How to Approach the Individualization of Treatment.

The "big data" in inflammatory bowel disease opens a route of detection of predictors that can determine the prognosis of each patient and allow the individualized selection of more efficient and safe therapeutic strategies. Immune biomarkers are a promising field to explore thoroughly.

Diet and microbiome in the beginning of the sequence of gut inflammation.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract due, at least partially, to an aberrant and excessive mucosal immune response to gut bacteria in genetically-predisposed individuals under certain environmental factors. The incidence of IBD is rising in western and newly industrialized countries, paralleling the increase of westernized dietary patterns, through new antigens, epithelial function and permeability, epigenetic mechanisms (e.g., DNA methylation), and alteration of the gut microbiome. Alteration in the composition and functionality of the gut microbiome (including bacteria, viruses and fungi) seems to be a nuclear pathogenic factor. The microbiome itself is dynamic, and the changes in food quality, dietary habits, living conditions and hygiene of these western societies, could interact in a complex manner as modulators of dysbiosis, thereby influencing the activation of immune cells' promoting inflammation. The microbiome produces diverse small molecules via several metabolic ways, with the fiber-derived short-chain fatty acids (i.e., butyrate) as main elements and having anti-inflammatory effects. These metabolites and some micronutrients of the diet (i.e., vitamins, folic acid, beta carotene and trace elements) are regulators of innate and adaptive intestinal immune homeostasis. An excessive and unhealthy consumption of sugar, animal fat and a low-vegetable and -fiber diet are risk factors for IBD appearance. Furthermore, metabolism of nutrients in intestinal epithelium and in gut microbiota is altered by inflammation, changing the demand for nutrients needed for homeostasis. This role of food and a reduced gut microbial diversity in causing IBD might also have a prophylactic or therapeutic role for IBD. The relationship between dietary intake, symptoms, and bowel inflammation could lead to dietary and lifestyle recommendations, including diets with abundant fruits, vegetables, olive oil and oily fish, which have anti-inflammatory effects and could prevent dysbiosis and IBD. Dietary modulation and appropriate exclusion diets might be a new complementary management for treatment at disease flares and in refractory patients, even reducing complications, hospitalizations and surgery, through modifying the luminal intestinal environment.

Sleep Quality, Quality of Life, and Patient-Reported Outcomes.

Measuring health outcomes through patient-reported outcomes is a feasible scenario in the short term, more human, and more linked to the situation that the patient cares about, overcoming limitations of the classic activity scores.

EpidemIBD: rationale and design of a large-scale epidemiological study of inflammatory bowel disease in Spain.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with a considerable burden to the patient and society. However, current data on IBD incidence and burden are limited because of the paucity of nationwide epidemiological studies, heterogeneous designs, and a low number of participating centers and sample size. The EpidemIBD study is a large-scale investigation to provide an accurate assessment of the incidence of IBD in Spain, as well as treatment patterns and outcomes. METHODS: This multicenter, population-based incidence cohort study included patients aged >18 years with IBD (Crohn's disease, ulcerative colitis, or unclassified IBD) diagnosed during 2017 in 108 hospitals in Spain, covering 50% of the Spanish population. Each participating patient will attend 10 clinic visits during 5 years of follow up. Demographic data, IBD characteristics and family history, complications, treatments, surgeries, and hospital admissions will be recorded. RESULTS: The EpidemIBD study is the first large-scale nationwide study to investigate the incidence of IBD in Spain. Enrollment is now completed and 3627 patients are currently being followed up. CONCLUSIONS: The study has been designed to overcome many of the limitations of previous European studies into IBD incidence by prospectively recruiting a large number of patients from all regions of Spain. In addition to epidemiological information about the burden of IBD, the 5-year follow-up period will also provide information on treatment patterns, and the natural history and financial burden of IBD.

Quality of life during one year of postoperative prophylactic drug therapy after intestinal resection in Crohn's patients: Results of the APPRECIA trial.

BACKGROUND: In APPRECIA trial, Crohn's disease (CD) patients undergoing intestinal resection were randomized to postoperative adalimumab (ADA) or azathioprine (AZA). AIMS: To evaluate health-related quality of life (HRQoL) in APPRECIA trial. METHODS: HRQoL was evaluated using disease-specific shortened Spanish version of the IBDQ (SIBDQ-9) and generic European Quality of Life-5 Dimensions (EQ-5D) questionnaires, completed at baseline and at weeks 24 and 52. RESULTS: Sixty-one patients (37 ADA and 24 AZA) had evaluable data for HRQoL. Patients treated with ADA or AZA had significant improvement from baseline to weeks 24 and 52 in SIBDQ-9 and EQ-5D (p < 0.001 and p ≤ 0.006 for all comparisons, respectively). There were no differences between treatment arms in mean change in SIBDQ-9 and EQ-5D at weeks 24 and 52 vs baseline. Only patients without endoscopic recurrence had significant improvement in SIBDQ-9 (p < 0.001) and EQ-5D (p < 0.001) at week 52. At week 52, there was a high to moderate negative correlation between CDAI score with SIBDQ-9 score (Pearson's r: -0.768) and with EQ-5D index (r: -0.644). CONCLUSION: HRQoL improved after intestinal resection in CD, irrespective of the postoperative therapy used (ADA or AZA). Outcomes in HRQoL were associated with prevention of endoscopic recurrence, since improvements in HRQoL were only significant in patients with endoscopic remission at 1 year.

Rapidity of clinical response to adalimumab and improvement of quality of life in luminal Crohn's disease: RAPIDA study / Rapidez de la respuesta clínica a adalimumab y mejora de la calidad de vida en la enfermedad de Crohn luminal: estudio RAPIDA

Objective: No studies evaluating the rapidity of response to biological therapies are available for Crohn's disease (CD). The aim of this study was to evaluate rapidity of onset of clinical response and impact on quality of life (QoL) of adalimumab therapy in adult anti-TNF-naïve patients with moderately-to-severely active CD.Patients and methods: RAPIDA was an open-label, single-arm, prospective, multicenter clinical trial. Adult patients with moderately-to-severely active luminal CD, anti-TNF-naïve, and unresponsive to conventional therapy were treated with adalimumab. Clinical disease activity, QoL and inflammatory biomarkers were measured at day 4, and weeks 1, 2, 4, and 12 after treatment initiation. Results: Eighty-six patients were included in the intention-to-treat (ITT) analyses. Clinical disease activity was reduced from a median of 9.0 points to 6.0 points at day 4. Clinical response (≥ 3-point reduction in the Harvey-Bradshaw Index, HBI) was achieved by 61.6% (d4) and 75.6% (w1) of patients in the ITT population (median 2.5 days) and with non-responder imputation (NRI), by 55.8% and 53.4%, respectively. The proportion of patients in clinical remission (HBI<5) at weeks 2 and 4 in the ITT population was 54.7% and 62.8%, respectively (median 7.0 days), and 38.4% and 45.3% in the NRI population. All QoL scores significantly improved and inflammatory biomarkers significantly decreased from day 4 onwards (p<0.0001).Conclusion: Rapid clinical response and remission, improvement in QoL and fatigue, and a reduction of inflammatory biomarkers were achieved with adalimumab as early as day 4 in adult anti-TNF-naïve patients with moderately-to-severely active CD. (AU)

Objetivo: No hay estudios que evalúen la rapidez de la respuesta a las terapias biológicas en la enfermedad de Crohn (EC). El objetivo fue evaluar la rapidez del inicio de la respuesta clínica y el impacto en la calidad de vida (CdV) de la terapia con adalimumab en pacientes adultos con EC moderada-grave. Pacientes y métodos: RAPIDA fue un ensayo clínico abierto, de un solo brazo, prospectivo y multicéntrico. Se trató con adalimumab a pacientes adultos con EC luminal activa moderada-grave, sin tratamiento previo con anti-TNF y sin respuesta a terapia convencional. Se midieron la actividad clínica de la enfermedad, la CdV y los biomarcadores inflamatorios el día 4 y las semanas 1, 2, 4 y 12 tras el tratamiento.Resultados: Se incluyeron 86 pacientes en los análisis por intención de tratar (IdT). La actividad clínica de la enfermedad se redujo de una mediana de 9,0 a 6,0 puntos en el día 4. La respuesta clínica (reducción ≥3 puntos en el Índice Harvey-Bradshaw, IHB) se dio en un 61,4% (d4) y un 75,6% (s1) de los pacientes IdT y en un 55,8% y un 53,4% con imputación de no respondedores (INR). La proporción de pacientes IdT en remisión clínica (IHB<5) en las s2 y s4 fue de 54,7% y 62,8%, respectivamente, y 38,4% y 45,3% en la población INR. Todas las puntuaciones de CdV mejoraron significativamente y los biomarcadores inflamatorios disminuyeron significativamente desde el día 4 (p<0,0001).Conclusiones: Se logró una rápida respuesta clínica y remisión, mejoría en la CdV y fatiga, y una reducción de los biomarcadores inflamatorios en los pacientes tratados con adalimumab ya en el día 4. (AU)

Adalimumab vs Azathioprine in the Prevention of Postoperative Crohn's Disease Recurrence. A GETECCU Randomised Trial.

BACKGROUND AND AIMS: Postoperative recurrence of Crohn's disease [POR-CD] is almost certain if no prophylaxis is administered. Evidence for optimal treatment is lacking. Our aim was to compare the efficacy of adalimumab [ADA] and azathioprine [AZA] in this setting. METHODS: We performed a phase 3, 52-week, multicentre, randomised, superiority study [APPRECIA], in which patients with ileocolonic resection were randomised either to ADA 160-80-40 mg subcutaneously [SC] or AZA 2.5 mg/kg/day, both associated with metronidazole. The primary endpoint was endoscopic recurrence at 1 year [Rutgeerts i2b, i3, i4], as evaluated by a blinded central reader. RESULTS: We recruited 91 patients [median age 35.0 years, disease duration 6.0 years, 23.8% smokers, 7.1% previous resections]. The study drugs were administered to 84 patients. Treatment was discontinued owing to adverse events in 11 patients [13.1%]. Discontinuation was significantly less frequent in the ADA [4.4%] than in the AZA group [23.2%] (dif.: 18.6% [95% CI 4.1-33.2], p = 0.011). According to the intention-to-treat analysis, therapy failed in 23/39 patients in the AZA group [59%] and 19/45 patients in the ADA group [42.2%] [p = 0.12]. In the per-protocol analysis [61 patients with centrally evaluable images], recurrence was recorded in 8/24 [33.3%] patients in the AZA and 11/37 [29.7%] in the ADA group [p = 0.76]. No statistically significant differences between the groups were found for recurrence in magnetic resonance images, biological markers of activity, surgical procedures, or hospital admissions. CONCLUSIONS: ADA has not demonstrated a better efficacy than AZA [both associated with metronidazole] for prophylaxis of POR-CD in an unselected population, although tolerance to ADA is significantly better. ClinicalTrials.gov NCT01564823.

Ozone Therapy in the Management of Persistent Radiation-Induced Rectal Bleeding in Prostate Cancer Patients.

Introduction. Persistent radiation-induced proctitis and rectal bleeding are debilitating complications with limited therapeutic options. We present our experience with ozone therapy in the management of such refractory rectal bleeding. Methods. Patients (n = 12) previously irradiated for prostate cancer with persistent or severe rectal bleeding without response to conventional treatment were enrolled to receive ozone therapy via rectal insufflations and/or topical application of ozonized-oil. Ten (83%) patients had Grade 3 or Grade 4 toxicity. Median follow-up after ozone therapy was 104 months (range: 52-119). Results. Following ozone therapy, the median grade of toxicity improved from 3 to 1 (p < 0.001) and the number of endoscopy treatments from 37 to 4 (p = 0.032). Hemoglobin levels changed from 11.1 (7-14) g/dL to 13 (10-15) g/dL, before and after ozone therapy, respectively (p = 0.008). Ozone therapy was well tolerated and no adverse effects were noted, except soft and temporary flatulence for some hours after each session. Conclusions. Ozone therapy was effective in radiation-induced rectal bleeding in prostate cancer patients without serious adverse events. It proved useful in the management of rectal bleeding and merits further evaluation.

Resources Utilization and Costs the Year Before and After Starting Treatment with Adalimumab in Crohn's Disease Patients.

BACKGROUND: This study examines the resources utilization in patients with Crohn's disease (CD) during the year before (Y - 1) and after (Y + 1) starting treatment with adalimumab and the drug's efficiency. METHODS: Observational, multicenter, prospective cohort study of patients with CD naive to biological drugs. The proportion of patients with CD Activity Index (CDAI) <150 was considered as the effectiveness variable. Costs considered were direct costs (DC) related to the use of health care resources, and indirect costs (IC) related to sick leave in Y - 1 and Y + 1. Adalimumab efficiency was estimated as the incremental cost/effectiveness ratio. A deterministic sensitivity analysis was performed building 3 scenarios: base case, the least favorable, and the most favorable case for adalimumab. RESULTS: In the cohort of 126 patients (50.8% men; age 39.1 ± 13.8 yr), the proportion of patients in remission increased from 34.1% by the end of Y - 1 to 83.3% by the end of Y + 1. Although the DC increase by the use of adalimumab, the use of doctor visits, emergency room visits, laboratory tests, diagnostic examinations, and nonbiological drug treatment were lower (P < 0.05) in Y + 1 than Y - 1. In the base case scenario, considering only DC, the incremental cost/effectiveness ratio was €31,308 and including IC, it was €28,936. In patients with CDAI > 150 at the onset, incremental cost/effectiveness ratio was €20,119 and €18,223, considering DC alone or included IC, respectively. CONCLUSIONS: In patients with CD, adalimumab increases pharmacological costs at the expense of biological therapy but reduces the cost of other drugs, the use of health care resources, and IC. Adalimumab efficiency is 30% greater in patients with CDAI > 150.