Iron therapy supplementation in inflammatory bowel disease patients with iron deficiency anemia: findings from a real-world analysis in Italy.

BACKGROUND: This real-world analysis evaluated iron therapy supplementation in inflammatory bowel disease patients with iron-deficiency anemia, considering disease progression and healthcare resource consumption. METHODS: A retrospective observational study was conducted using administrative databases of a pool of Italian healthcare entities, covering about 9.3 million beneficiaries. Between January 2010 and September 2017, adult patients were enrolled in the presence of either hospitalization or active exemption code for ulcerative colitis/Crohn's disease, or one vedolizumab prescription. Iron-deficiency anemia was identified by at least one prescription for iron and/or hospitalization for iron-deficiency anemia and/or blood transfusion (proxy of diagnosis). Patients were divided in untreated and iron-treated during 12-month follow-up and analyzed before and after propensity score matching. Disease progression, was evaluated through inflammatory bowel disease-related hospitalizations and surgeries, and healthcare resource utilization was assessed. RESULTS: Overall, 1753 patients were included, 1077 (61.4%) treated with iron therapy and 676 (38.6%) untreated. After propensity score matching, 655 patients were included in each group. In unbalanced cohorts, disease progression was significantly reduced in patients receiving iron therapy compared to the untreated (11.0% vs. 15.7%, P  < 0.01), and this trend was maintained also after applying propensity score matching. The overall mean cost/patient was significantly lower in iron-treated than untreated (4643€ vs. 6391€, P  < 0.01). CONCLUSION: The findings of this real-world analysis suggest that iron therapy was associated with significant benefits in inflammatory bowel disease patients with iron-deficiency anemia, in terms of both disease progression and healthcare resource utilization.

Indications and hemoglobin thresholds for red blood cell transfusion and iron replacement in adults with gastrointestinal bleeding: An algorithm proposed by gastroenterologists and patient blood management experts.

Gastrointestinal (GI) bleeding is associated with considerable morbidity and mortality. Red blood cell (RBC) transfusion has long been the cornerstone of treatment for anemia due to GI bleeding. However, blood is not devoid of potential adverse effects, and it is also a precious resource, with limited supplies in blood banks. Nowadays, all patients should benefit from a patient blood management (PBM) program that aims to minimize blood loss, optimize hematopoiesis (mainly by using iron replacement therapy), maximize tolerance of anemia, and avoid unnecessary transfusions. Integration of PBM into healthcare management reduces patient mortality and morbidity and supports a restrictive RBC transfusion approach by reducing transfusion rates. The European Commission has outlined strategies to support hospitals with the implementation of PBM, but it is vital that these initiatives are translated into clinical practice. To help optimize management of anemia and iron deficiency in adults with acute or chronic GI bleeding, we developed a protocol under the auspices of the Spanish Association of Gastroenterology, in collaboration with healthcare professionals from 16 hospitals across Spain, including expert advice from different specialties involved in PBM strategies, such as internal medicine physicians, intensive care specialists, and hematologists. Recommendations include how to identify patients who have anemia (or iron deficiency) requiring oral/intravenous iron replacement therapy and/or RBC transfusion (using a restrictive approach to transfusion), and transfusing RBC units 1 unit at a time, with assessment of patients after each given unit (i.e., "don't give two without review"). The advantages and limitations of oral versus intravenous iron and guidance on the safe and effective use of intravenous iron are also described. Implementation of a PBM strategy and clinical decision-making support, including early treatment of anemia with iron supplementation in patients with GI bleeding, may improve patient outcomes and lower hospital costs.

Multi-target Treatment for Irritable Bowel Syndrome with STW 5: Pharmacological Modes of Action.

Irritable bowel syndrome (IBS) is a heterogeneous and complex functional gastrointestinal disorder with a global prevalence of approximately 11% and high geographic variation. IBS encompasses various symptom clusters considered to reflect complex patho-etiological mechanisms, and effective treatment options are limited, with most medications targeting individual mechanisms and symptoms. Therefore, multi-targeted treatment is required. IBS is currently viewed as a disorder of disturbed gut-brain interactions with abnormalities at different sites along the gut-brain axis, including altered gastrointestinal motility, visceral hypersensitivity, increased intestinal permeability, and altered gut microbiota. All of these abnormalities represent individual targets for STW 5, a herbal preparation with nine different extracts indicated for the treatment of functional dyspepsia and IBS. As a multi-targeted medicinal drug, STW 5 possesses multiple pharmacodynamic effects. Several in vitro and in vivo studies have demonstrated STW 5 efficacy on numerous IBS patho-mechanisms targeting gastrointestinal smooth muscles, visceral afferent nerves, inflammation, gut permeability, and the gut microbiome.

Use of Evidence-Based Herbal Medicines for Patients with Functional Gastrointestinal Disorders: A Conceptional Framework for Risk-Benefit Assessment and Regulatory Approaches.

BACKGROUND: Herbal or complementary medicines are frequently used for the treatment of patients with functional gastrointestinal disorders (FGID). Regulatory requirements for herbal therapies are inconsistent and, in many jurisdictions, herbal therapies are either self-, minimally- or unregulated. AIM: To provide guidance for the appropriate and safe use of herbal medicines in patients with FGID patients with special consideration of the regulatory frameworks. METHODS: A PubMed search of the literature was performed; relevant articles were included. RESULTS: Similar to chemically defined therapies herbal medicines can cause adverse events. Thus, a risk-benefit appraisal should be undertaken for these therapies. While there is no disease specific mortality in FGID patients, patients with FGID who fail to respond to "empiric" chemically defined therapies undergo diagnostic and therapeutic measures that can be associated with appreciable morbidity and mortality. Thus, effective herbal treatments that subsequently reduce health-care utilization, reduce risks related to diagnostic or therapeutic measures that are initiated if no improvement of symptoms occurs. This "protective" effect of effective treatments for FGID needs to be taken in consideration when the risks and benefits of treatments are determined. In addition, standards that mirror regulations for chemically defined treatments should apply and the components of the respective preparations should undergo ongoing toxicological testing and rigorous quality assurance measures (including pharmacovigilance) applied. CONCLUSIONS: Some herbal therapies offer significant benefits for patients with FGID. To ensure the safety of these treatments, the regulatory requirements should mirror requirements for chemically defined treatments.

Trastornos funcionales y motores digestivos / Functional and motor gastrointestinal disorders

En este artículo se comentan las comunicaciones más interesantes que se han presentado en el congreso americano, durante la Digestive Disease Week celebrada en San Diego, en el área de las alteraciones motoras y los trastornos funcionales digestivos. Sin ninguna duda, una de las comunicaciones más relevantes fue la presentación de los nuevos criterios diagnósticos de los trastornos funcionales digestivos según el consenso de Roma IV. Por ello se dedica una parte del texto a explicar cómo son estos nuevos criterios en los trastornos funcionales más frecuentes. De hecho, se comentan ya datos que comparan los criterios de Roma IV y Roma III en el diagnóstico del síndrome del intestino irritable, comprobando que los nuevos criterios son algo más restrictivos. Desde el punto de vista fisiopatológico hay varios trabajos que demuestran que la agregación de alteraciones fisiopatológicas comporta una mayor gravedad sintomática en distintos trastornos funcionales. Desde el punto de vista terapéutico se aportan más datos sobre la eficacia y mecanismos de acción de acotiamida en la dispepsia funcional, de eficacia y seguridad de domperidona en pacientes con gastroparesia y de eficacia de linaclotida, tanto en intestino irritable como en estreñimiento. Siguiendo con el síndrome del intestino irritable, vuelven a presentarse más resultados favorables a la dieta baja en FODMAP que hacen énfasis en su papel sobre las modificaciones de la microbiota. Finalmente, también se presentaron datos de eficacia a largo plazo de las distintas opciones de tratamiento de la acalasia

This article discusses the most interesting presentations at Digestive Disease Week, held in San Diego, in the field of functional and motor gastrointestinal disorders. One of the most important contributions was undoubtedly the presentation of the new Rome IV diagnostic criteria for functional gastrointestinal disorders. We therefore devote some space in this article to explaining these new criteria in the most common functional disorders. In fact, there has already been discussion of data comparing Rome IV and Rome III criteria in the diagnosis of irritable bowel syndrome, confirming that the new criteria are somewhat more restrictive. From the physiopathological point of view, several studies have shown that the aggregation of physiopathological alterations increases symptom severity in distinct functional disorders. From the therapeutic point of view, more data were presented on the efficacy of acotiamide and its mechanisms of action in functional dyspepsia, the safety and efficacy of domperidone in patients with gastroparesis, and the efficacy of linaclotide both in irritable bowel syndrome and constipation. In irritable bowel syndrome, more data have come to light on the favourable results of a low FODMAP diet, with emphasis on its role in modifying the microbiota. Finally, long-term efficacy data were presented on the distinct treatment options in achalasia

The low-FODMAP diet for irritable bowel syndrome: Lights and shadows / Dieta con bajo contenido en FODMAP para el síndrome del intestino irritable: luces y sombras

Irritable bowel syndrome (IBS) affects 10-15% of the western population. Drug therapy for this entity has shown limited efficacy. The low Fermentable Oligo-, Di-, Monosaccharides And Polyols (FODMAP) diet has recently emerged as an effective intervention for reducing gastrointestinal symptoms in IBS. Currently, several mechanistic studies have proven the rational basis of carbohydrate restriction. In addition, high-quality evidence (prospective studies and randomized controlled trials) from a variety of countries supports the high effectiveness of a low-FODMAP diet for IBS symptoms (70%), especially abdominal bloating, pain, and diarrhea. Importantly, this diet seems to be superior to a gluten-free diet for patients with non-celiac gluten sensitivity. The most controversial features of the low FODMAP diet are its short- and long-term limitations (a high level of restriction, the need for monitoring by an expert dietitian, potential nutritional deficiencies, significant gut microbiota reduction, lack of predictors of response), as well as the potential lack of advantage over alternative dietary, pharmacological and psychological interventions for IBS. Although liberalization of carbohydrate intake is recommended in the long-term, the reintroduction process remains to be clarified as, theoretically, global carbohydrate restriction is deemed to be necessary to avoid additive effects

El síndrome de intestino irritable (SII) es una entidad clínica que afecta al 10-15% de la población occidental, para la que los fármacos disponibles han demostrado una eficacia limitada. La dieta con bajo contenido en oligo, di, monosacáridos y polioles (FODMAP) ha surgido recientemente como una medida eficaz para el control de los síntomas gastrointestinales del SII. En la actualidad, los estudios fisiopatológicos han confirmado la base racional de la restricción de carbohidratos en el SII y existe evidencia científica de alta calidad (estudios prospectivos y ensayos clínicos controlados) proveniente de diversos países confirmado la eficacia de la dieta con bajo contenido en FODMAP para el SII (70%), especialmente para la hinchazón y dolor abdominal, así como la diarrea. Cabe destacar que esta dieta parece ser más eficaz que la dieta sin gluten para los pacientes con sensibilidad al gluten no celíaca. Los aspectos más controvertidos de esta dieta son las limitaciones que implica a corto y largo plazo (nivel alto de restricción alimentaria, la necesidad de monitorización por dietistas, riesgo de déficits nutricionales, una descenso marcado de la microbiota intestinal, la ausencia de herramientas predictoras de respuesta), al igual que una eficacia similar a otras intervenciones dietéticas menos restrictivas, farmacológicas y psicológicas en recientes estudios. Pese a que se recomienda liberalizar el consumo de carbohidratos a largo plazo, queda por dilucidar con exactitud la estrategia de reintroducción, ya que teóricamente el éxito de la dieta reside en una restricción global de carbohidratos para evitar efectos aditivos

[Functional and motor gastrointestinal disorders]. / Trastornos funcionales y motores digestivos.

This article discusses the most interesting studies on functional and motor gastrointestinal disorders presented at Digestive Diseases Week (DDW), 2015. Researchers are still seeking biomarkers for irritable bowel syndrome and have presented new data. One study confirmed that the use of low-dose antidepressants has an antinociceptive effect without altering the psychological features of patients with functional dyspepsia. A contribution that could have immediate application is the use of transcutaneous electroacupuncture, which has demonstrated effectiveness in controlling nausea in patients with gastroparesis. New data have come to light on the importance of diet in irritable bowel syndrome, although the effectiveness of a low-FODMAP diet seems to be losing momentum with time. Multiple data were presented on the long-term efficacy of rifaximin therapy in patients with irritable bowel syndrome and diarrhoea. In addition, among other contributions, and more as a curiosity, a study evaluated the effect of histamine in the diet of patients with irritable bowel syndrome.

Anaemia management in patients with inflammatory bowel disease: routine practice across nine European countries.

BACKGROUND AND OBJECTIVES: Anaemia and iron deficiency (ID) are common complications in inflammatory bowel disease (IBD). In patients undergoing iron therapy, intravenous iron supplementation is recommended in preference to oral therapy. This study evaluated routine practice in the management of IBD-associated anaemia and ID to verify implementation of international treatment guidelines. MATERIALS AND METHODS: Gastroenterologists from nine European countries (n=344) were surveyed about their last five IBD patients treated for anaemia (n=1404). Collected information included tests performed at anaemia diagnosis, haemoglobin (Hb) levels and iron status parameters, the anaemia treatment given and, if applicable, the iron administration route. RESULTS: Selection of diagnostic tests and treatment for IBD-associated anaemia varied considerably across Europe. Anaemia and iron status were mainly assessed by Hb (88%) and serum ferritin (75%). Transferrin saturation was only tested in 25% of patients. At diagnosis of anaemia, 56% presented with at least moderate anaemia (Hb<10 g/dl) and 15% with severe anaemia (Hb<8 g/dl). ID (ferritin<30 ng/ml) was detected in 76%. Almost all patients (92%) received iron supplementation; however, only 28% received intravenous iron and 67% oral iron. Management practice was similar in 2009 and 2011. CONCLUSION: In clinical practice, most IBD patients received oral iron even though this administration route may aggravate the disease, and despite international guidelines recommending intravenous administration as the preferred route. The high frequency of ID suggests insufficient monitoring of iron status in IBD patients. There is a need to increase awareness and implementation of international guidelines on iron supplementation in patients with IBD.

One year intermittent rifaximin plus fibre supplementation vs. fibre supplementation alone to prevent diverticulitis recurrence: a proof-of-concept study.

BACKGROUND: Evidence supporting appropriate medical therapy to prevent recurrence of colonic diverticulitis is limited. Our goal was to evaluate the potential of rifaximin given periodically in addition to fibre for the prophylaxis of recurrences. METHODS: We conducted a multicentre, randomized, open controlled study in patients with a recent episode of colonic diverticulitis, currently in remission. Patients received 3.5 g of high-fibre supplementation b.d. with or without one week per month of the non-absorbable antibiotic rifaximin (400 mg b.d.) for 12months. Primary endpoint was recurrence of diverticulitis, encompassing acute symptomatic flare with or without complications, analyzed by multivariable logistic regression analysis and by Cox proportional hazard method. RESULTS: After randomizing 165 patients, the study was interrupted since the recruitment rate was largely below the minimum anticipated, and the trial was switched from evidence-gathering to proof-of-concept. Recurrences occurred in 10.4% of patients given rifaximin plus fibres vs. 19.3% of patients receiving fibres alone. The logistic analysis adjusted for sex, age, illness duration, time from last episode, disease localization and centre recruitment rate, yielded a significant treatment effect (odds ratio 3.20; 95% confidence interval: 1.16-8.82; P=0.025). Patients with diverticulitis diagnosed since ≥1 year receiving rifaximin also had a lower incidence of recurrences (10%; 95% confidence interval: 2-47% vs. 67%; 95% confidence interval: 37-100%). Both treatments were safe. CONCLUSIONS: This study represents a proof-of concept of the efficacy of cyclic rifaximin treatment, added to fibre supplements, to reduce the risk of recurrences of diverticulitis in patients in remission.

[Treatment of oropharyngeal dysphagia with neuromuscular electrostimulaiton]. / Tratamiento con electroestimulación neuromuscular de la disfagia orofaríngea en pacientes con ictus.

BACKGROUND AND OBJECTIVE: Oropharyngeal dysphagia is highly prevalent in stroke patients, with a high mortality and morbidity. Neuromuscular electrostimulation (NMES) is a new and potentially useful therapy. We assessed the therapeutic effectiveness and safety of NMES in the treatment of oropharyngeal dysphagia in patients with stroke. PATIENTS AND METHOD: Prospective study of stroke patients, with tracheal aspiration revealed by videofluoroscopy (VDF), who underwent conventional therapy of oropharyngeal dysphagia as well as NMES. We did a follow-up at the end of the treatment and 3 months later. RESULTS: Patients underwent 18 courses of treatment (15-20) with a mean stimulation intensity of 12.45mA (range: 6.6-16.7mA). Before starting therapy, 8 patients were fed exclusively by means of a gastrostomy tube; after the treatment, only one patient needed it. No patient had complications. VDF parameters before treatment: oral transition time, swallowing reflex shooting (SRS) and pharyngeal transition time were longer and the hyoid elevation was reduced. After the treatment, the number of patients with tracheal aspiration decreased to 6, but only in 6 it persisted for the three analyzed viscosities (liquid, nectar and pudding), with an overall improvement of the VDF parameters. The only predictive factor of therapeutic effectiveness was the delay in the SRS. CONCLUSION: NMES is an effective and safe treatment for stroke patients with oropharyngeal dysphagia.

Effect of sacral anterior root stimulator on bowel dysfunction in patients with spinal cord injury.

PURPOSE: Bowel dysfunction is a problem in patients with spinal cord injury. The sacral anterior root stimulator has been used for neurogenic bladder and has been claimed to be useful for neurogenic bowel. The purposes of this study were to analyze the clinical response of bowel function to the sacral anterior root stimulator and to evaluate physiologic factors that could determine its efficacy. METHODS: Eighteen consecutive patients with spinal cord injury and an implanted sacral anterior root stimulator were evaluated. Clinical assessment, colonic transit time, and anorectal manometry were performed. Patients were evaluated before implantation of the sacral anterior root stimulator and clinically reevaluated after 12 months. RESULTS: Fewer patients required laxatives after implantation of the sacral anterior root stimulator. The mean number of methods used to evacuate was reduced from 2.1 to 1.5 (P < 0.05). Bowel movement frequency was higher (P < 0.05). Time devoted to defecation was reduced, although no statistical significance was achieved. Fecal incontinence did not change, but constipation was reduced (P < 0.05). Most patients reported being more satisfied with bowel function after implantation of the sacral anterior root stimulator. No correlation was found between objective and subjective responses to the sacral anterior root stimulator and manometric or colonic transit times before implantation. CONCLUSION: The sacral anterior root stimulator improves bowel function, and patient satisfaction with this treatment is high. Further studies are needed to evaluate the characteristics of stimulation parameters to achieve better results.