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.

Iron deficiency anemia impacts disease progression and healthcare resource consumption in patients with inflammatory bowel disease: a real-world evidence study.

Background: Iron deficiency anemia (IDA) is a common extraintestinal manifestation of inflammatory bowel disease (IBD), affecting around one-third of patients. Objective: To compare IBD progression and healthcare resource utilization in patients with and without a co-diagnosis of IDA in a real-world setting. Design: A retrospective comparative study was conducted using Italian entities' administrative databases, covering 9.3 million health-assisted individuals. Methods: Adult IBD patients diagnosed with ulcerative colitis and/or Crohn's disease were enrolled between January 2010 and September 2017. Within 12 months from IBD diagnosis, IDA was identified by at least one prescription for iron and/or IDA hospitalization and/or blood transfusion (proxy of diagnosis). IBD population was divided according to the presence/absence of IDA. Given the nonrandom patients' allocation, propensity score matching (PSM) was applied to abate potential unbalances between the groups. Before and after PSM, IBD progression (in terms of IBD-related hospitalizations and surgeries), and healthcare resource costs were assessed. Results: Overall, 13,475 IBD patients were included, with an average age at diagnosis of 49.9 years, and a 53.9% percentage of male gender. Before PSM, 1753 (13%) patients were IBD-IDA, and 11,722 (87%) were IBD-non-IDA. Post-PSM, 1753 IBD-IDA patients were matched with 3506 IBD-non-IDA. Before PSM, IBD progression was significantly higher in IBD-IDA (12.8%) than in IBD-non-IDA (6.5%) (p < 0.001). After PSM, IBD progression and IBD-related hospitalizations were significantly (p < 0.001) more frequent in IBD-IDA patients (12.8% and 12.0%, respectively) compared to IBD-non-IDA (8.7% and 7.7%). Consistently, healthcare expenditures resulted significantly higher among IDA patients (p < 0.001), with an overall mean annual cost of €5317 compared to €2798 for patients without IDA. These results were confirmed after PSM matching, as the mean annual total cost/patient in IBD-IDA versus IBD-non-IDA were €3693 and €3046, respectively (p < 0.001). Conclusion: In a real-life setting, IDA co-diagnosis in IBD patients was associated with disease progression and higher related economic burden.

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.

Relevance and needs of irritable bowel syndrome (IBS): Comparison with inflammatory bowel disease (IBD). (Please, if you are not interested in IBS, read it.). / Relevancia y necesidades del síndrome del intestino irritable (SII): comparación con la enfermedad inflamatoria intestinal (EII). (Por favor, si no te interesa el SII, léelo.).

INTRODUCTION: In our opinion there is an imbalance between the relevance of irritable bowel syndrome (IBS), and the resources that are provided. OBJECTIVE: To review the different factors that determine (or should determine) the interest of gastroenterologists in IBS, comparing it with inflammatory bowel disease (IBD). For this, 7 different areas have been analyzed: (1)Medical impact; (2)Social impact; (3)Academic importance; (4)Clinical relevance; (5)Scientific relevance; (6)Public relevance, and (7)Personal aspects of the doctor. RESULTS: The prevalence is 10 times higher in IBS, which represents up to 25% of gastroenterologist visits. Both pathologies alter the quality of life, in many cases in a similar way. The social cost is very important in both cases (e.g.: absenteeism of 21% and 18%) as well as the economic cost, although much higher in medication for IBD. Academic dedication is more than double for IBD, both in university and in MIR training. Scientific relevance is greater in IBD, with a number of publications four times higher. Public relevance is not very different between the two entities, although IBD patients are more associative. Doctors prefer IBD and tend to stigmatize IBS. CONCLUSION: In our opinion, to reduce this imbalance between needs and resources, human and material, in IBS it is essential to make drastic changes both in educational aspects, communication skills, prioritization according to the demands of patients, and reward (personal and social) of physicians.

Botulinum toxin type-A infiltration of the external anal sphincter to treat outlet constipation in motor incomplete spinal cord injury: pilot cohort study.

BACKGROUND: Outlet constipation is a major problem in spinal cord injury (SCI) patients. We aimed to study the efficacy of external anal sphincter (EAS) infiltration with type-A botulinum toxin (BTX-A) in motor incomplete SCI patients with outlet constipation. METHODS: Double blind, randomized, placebo controlled, comparative study in 16 motor incomplete SCI subjects. Patients were randomly assigned toreceive100 UI of BTX-A (n = 9) or physiologic serum infiltration (n = 7) in the EAS under electromyographic guidance. Outcome measures included a questionnaire for clinical bowel function evaluation, colonic transit time and anorectal manometry. All assessments were done at baseline, 1 and 3 months after treatment. RESULTS: Fourteen patients completed the study. In the BTX-A group we observed an improvement of subjective perception of bowel function (p = 0.01), constipation (p = 0.02) and neurogenic bowel dysfunction score (p = 0.02). The anorectal manometry revealed are duction of EAS voluntary contraction pressure (p = 0.01). No changes were observed in the placebo group. No significant side effects were observed in none of the groups. CONCLUSION: BTX-A infiltration of the EAS is a safe technique that in motor incomplete SCI, decreases the EAS contraction and the anal canal pressure during straining, and improves outlet constipation symptoms. Future studies in larger populations are needed.

Small intestinal bacterial overgrowth in spinal cord injury patients. / Sobrecrecimiento bacteriano del intestino delgado en pacientes con lesión medular.

AIM: Spinal cord injury (SCI) patients may have intestinal dysmotility and digestive symptoms that are associated with small intestinal bacterial overgrowth (SIBO). The aim of this study is to describe the prevalence of SIBO in SCI patients and the risk factors of its development. METHODS: Twenty-nine consecutive SCI patients were studied (10 women/19 men; mean age 47 years), 16 with subacute injuries (<9 months) and 13 with chronic injuries (>1 year). Nine patients were affected by tetraplegia and 15 by paraplegia. Each patient underwent a glucose breath test according to the North American Consensus and the presence of abdominal symptoms was evaluated during the test. The results were compared with 15 non-neurological patients with SIBO. RESULTS: Six patients tested positive for SIBO (21%), all of them affected by SCI in the subacute phase, 6/16 vs. 0/13 in the chronic phase (P<.05) and the majority with tetraplegia, 5/9 vs. 1/19 with paraplegia (P<.05). No statistically significant relationship was found with other clinical characteristics. All the tests were positive for methane or mixed (methane and hydrogen), while only 67% of the controls had methane-predominant production (P>.05). CONCLUSION: SCI patients can develop SIBO, more frequently in the subacute phase and in tetraplegic patients, highlighting a high production of methane. This complication should be considered in neurogenic bowel management.

Effectiveness of almagate in gastroesophageal reflux disease: a post-hoc analysis of a randomized cross-over double-blind study.

Almagate (aluminium-magnesium hydroxycarbonate hydrate) is a widely used antacid in Spain as an over-the-counter formulation. However, data on the control of acidity in patients with gastroesophageal reflux disease (GERD) are scarce. Herein we report a post-hoc analysis of a randomized crossover double-blind trial (ALR-006; data on file), in which equivalent single oral doses (1.5 g) of two formulations of almagate (AlmaxRetard® and Almax®, Laboratorios Almirall, Barcelona, Spain) were both effective for reflux esophagitis.

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.

Clinical response to linaclotide at week 4 predicts sustained response in irritable bowel syndrome with constipation and improvements in digestive and extra-digestive symptoms.

BACKGROUND: Linaclotide is approved for the treatment of moderate-to-severe irritable bowel syndrome (IBS) with constipation (IBS-C) in adults. This study aimed to assess factors predictive of a clinical response and improvements in non-IBS symptoms with linaclotide treatment in a Spanish patient population. METHODS: In this open-label phase IIIb study, patients with moderate-to-severe IBS-C received linaclotide 290 µg once daily for 12 weeks. The primary endpoint was clinical response at week 12, defined as >30% reduction in IBS symptom severity score (IBS-SSS) or IBS-SSS <75 plus self-reported response of feeling 'better' or 'much better' versus the baseline. Digestive nonintestinal and extra-digestive symptom scores were assessed. Baseline characteristics and week 4 clinical response were assessed as predictors of week 12 clinical response. RESULTS: A total of 96 patients were eligible; 91 were female and the mean age was 47.4 years. Mean (SD) baseline IBS-SSS was 371 (72.5). In the intention-to-treat and per-protocol populations, 22.9% and 31.7% were clinical responders at week 4, respectively, and 25.0% and 36.7% were clinical responders at week 12. Digestive nonintestinal and extra-digestive symptom scores were significantly improved at weeks 4 and 12. Baseline characteristic was not associated with week 12 clinical response; however, clinical response at week 4 was predictive of response at week 12 (OR: 6.5; 95%IC: 2.1-19.8). The most common adverse event was diarrhea inclusive of loose or watery stools (35.4%). CONCLUSIONS: Linaclotide improves IBS-C symptoms, including digestive nonintestinal and extra-digestive symptoms. A clinical response at week 4 may predict response at week 12.

Economic burden of moderate to severe irritable bowel syndrome with constipation in six European countries.

BACKGROUND: Irritable bowel syndrome with predominant constipation (IBS-C) is a complex disorder with gastrointestinal and nervous system components. The study aim was to assess the economic burden of moderate to severe IBS-C in six European countries (France, Germany, Italy, Spain, Sweden and the UK). METHODS: An observational, one year retrospective-prospective (6 months each) study of patients diagnosed in the last five years with IBS-C (Rome III criteria) and moderate to severe disease at inclusion (IBS Symptom Severity Scale score ≥ 175). The primary objective was to assess the direct cost to European healthcare systems. RESULTS: Five hundred twenty-five patients were included, 60% (range: 43.1-78.8%) suffered from severe IBS-C. During follow-up 11.1-24.0% of patients had a hospitalisation/emergency room (ER) visit, median stay range: 1.5-12.0 days and 41.1-90.4% took prescription drugs for IBS-C. 21.4-50.8% of employed patients took sick leave (mean: 11.6-64.1 days). The mean annual direct cost to the healthcare systems was €937.1- €2108.0. The total direct cost (combined costs to healthcare systems and patient) for IBS-C was €1421.7-€2487.1. CONCLUSIONS: IBS-C is not a life-threatening condition; however, it has large impact on healthcare systems and society. Direct and indirect costs for moderate to severe IBS-C were high with the largest direct cost driver being hospitalisations/ER visits.

A retrospective and prospective 12-month observational study of the socioeconomic burden of moderate to severe irritable bowel syndrome with constipation in Spain.

INTRODUCTION: The socioeconomic burden of irritable bowel syndrome with constipation (IBS-C) has never been formally assessed in Spain. PATIENTS AND METHODS: This 12-month (6-month retrospective and prospective periods) observational, multicentre study assessed the burden of moderate-to-severe IBS-C in Spain. Patients were included if they had been diagnosed with IBS-C (Rome III criteria) within the last 5 years and had moderate-to-severe IBS-C (IBS Symptom Severity Scale score [IBS-SSS] ≥175) at inclusion. The primary objective was to assess the direct cost to the Spanish healthcare system (HS). RESULTS: A total of 112 patients were included, 64 (57%) of which had severe IBS-C at inclusion. At baseline, 89 (80%) patients reported abdominal pain and distention. Patient quality of life (QoL), measured by the IBS-C QoL and EQ-5D instruments, was found to be impaired with a mean score of 59 and 57 (0-100, worst-best), respectively. Over the 6-month prospective period the mean IBS-C severity, measured using the IBS-SSS showed some improvement (315-234 [0-500, best-worst]). During the year, 89 (80%) patients used prescription drugs for IBS-C, with laxatives being the most frequently prescribed (n=70; 63%). The direct cost to the HS was €1067, and to the patient was €568 per year. The total direct cost for moderate-to-severe IBS-C was €1635. DISCUSSION: The majority of patients reported continuous IBS-C symptoms despite that 80% were taking medication to treat their IBS-C. Overall healthcare resource use and direct costs were asymmetric, with a small group of patients consuming the majority of resources.

International Consensus on Diverticulosis and Diverticular Disease. Statements from the 3rd International Symposium on Diverticular Disease.

The statements produced by the Chairmen and Speakers of the 3rd International Symposium on Diverticular Disease, held in Madrid on April 11th-13th 2019, are reported. Topics such as current and evolving concepts on the pathogenesis, the course of the disease, the news in diagnosing, hot topics in medical and surgical treatments, and finally, critical issues on the disease were reviewed by the Chairmen who proposed 39 statements graded according to level of evidence and strength of recommendation. Each topic was explored focusing on the more relevant clinical questions. The vote was conducted on a 6-point scale and consensus was defined a priori as 67% agreement of the participants. The voting group consisted of 124 physicians from 18 countries, and agreement with all statements was provided. Comments were added explaining some controversial areas.

The DICA Endoscopic Classification for Diverticular Disease of the Colon Shows a Significant Interobserver Agreement among Community Endoscopists: an International Study.

BACKGROUND AND AIMS: The Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification of diverticulosis and diverticular disease (DD) is currently available. It scores severity of the disease as DICA 1, DICA 2 and DICA 3. Our aim was to assess the agreement on this classification in an international endoscopists community setting. METHODS: A total of 96 doctors (82.9% endoscopists) independently scored a set of DD endoscopic videos. The percentages of overall agreement on DICA score and a free-marginal multirater kappa (κ) coefficient were reported as statistical measures of interrater agreement. RESULTS: Overall agreement in using DICA was 91.8% with a free-marginal kappa of 88% (95% CI 80-95). The overall agreement levels were: DICA 1, 85.2%; DICA 2, 96.5%; DICA 3, 99.5%. The free marginal κ was: DICA 1 = 0.753, DICA 2 = 0.958, DICA 3 = 0.919. The agreement about the main endoscopic items was 83.4% (k 67%) for diverticular extension, 62.6% (k 65%) for number of diverticula for each district, 86.8% (k 82%) for presence of inflammation, and 98.5 (k 98%) for presence of complications. CONCLUSIONS: The overall interrater agreement in this study ranges from good to very good. DICA score is a simple and reproducible endoscopic scoring system for diverticulosis and DD.

Hot Topics in Medical Treatment of Diverticular Disease: Evidence Pro and Cons.

Symptomatic Uncomplicated Diverticular Disease (SUDD) is the most common clinical form of Diverticular Disease (DD). The therapy should be aimed at reducing both the intensity and frequency of symptoms as well as preventing complications. The pharmacological treatments include fibers, not absorbable antibiotics (for example rifaximin), anti-inflammatory drugs (for example 5-amino-salycilic acid) and probiotics, alone or in combination with other drugs. Although some of these treatments seem to be effective in treating SUDD, but their efficacy in preventing complications of the disease is still uncertain. It has been hypothesized that microbial imbalance associated with bacterial overgrowth of the colon, may be the key to the development of diverticular disease (DD). Therefore, drugs that can manipulate gut microbiota such as probiotics or rifaximine are considered as a potential key therapy. Rifaximine is able to modulate the intestinal ecosystem, restoring eubiosis. Traditionally, DD of the colon is thought to be related to low grade of inflammation. By analogy with other inflammatory bowel diseases mesalazine has been studied also in DD. There are several evidences that may support the use of mesalazine in the SUDD. Unfortunately, mesalazine cannot be used to prevent diverticulitis because of the paucity of high-quality studies. Currently, mesalazine has a limited place for the management of SUDD. In SUDD probiotics have been proven as an effective therapy in reducing abdominal symptoms, but unfortunately there has been limited number of relevant studies regarding efficacy of this therapy.

Post-infectious IBS: Defining its clinical features and prognosis using an internet-based survey.

BACKGROUND: Gastrointestinal infection is an important risk factor for developing irritable bowel syndrome (IBS). Our aim was to characterise post-infectious IBS (PI-IBS) compared to other IBS patients. METHODS: An internet survey of IBS patients using Rome III diagnostic questionnaire, Hospital Anxiety and Depression Scale (HADS) and Patient Health Questionnaire-12 Somatic Symptom (PHQ12-SS) scale score documenting the mode of onset was conducted. RESULTS: A total of 7811 participants (63.2% female), of whom 1004 (13.3%) met criteria for PI-IBS, were studied. Seventy per cent of PI-IBS patients described sudden onset, 35% onset while travelling, 49.6% vomiting, 49.9% fever and 20.3% bloody diarrhoea. Compared to other IBS individuals, PI-IBS was significantly associated with living in Northern Europe and North America, having a hysterectomy, not having an appendicectomy, higher PHQ12-SS score and having more than one toilet in the family home. PI-IBS patients had more frequent stools. At one year recovery rate in the PI-IBS and non-PI-IBS group was 19.7% and 22.2%, p = 0.15. Recovery rates were lower for females (20.7%) vs males (38.8%), those with somatisation (23.0%) vs those without (33.2%) and those living in North America or Northern Europe (21.1%) vs living elsewhere (33.9%) p ≤ 0.001. CONCLUSION: PI-IBS accounts for around 13% of all IBS in this internet sample, with some distinctive features but a similar prognosis to the remainder.

Irritable bowel syndrome: How to improve decision making in clinical practice. / Síndrome del intestino irritable: cómo mejorar la toma de decisiones en la práctica clínica.

Irritable bowel syndrome (IBS) is a highly prevalent functional disorder, characterised by the presence of recurrent abdominal pain associated with changes in bowel habits. Its physiopathology is complex, its clinical manifestations are diverse, and the therapeutic possibilities are multiple and not well known. In clinical practice, the diagnosis of IBS represents an important challenge; this means that in many cases the patients do not receive the proper diagnosis, which implies an absence of a targeted treatment, and therefore bad symptomatic control. In this article, the fundamental questions posed by the doctor when dealing with a patient with symptoms compatible with IBS are presented chronologically. The main objective is to provide clinical and eminently practical information that facilitates the management of patients with IBS, from both diagnostic and therapeutic points of view.

Open questions and misconceptions in the diagnosis and management of anemia in patients with gastrointestinal bleeding. / Preguntas y errores en el diagnóstico y manejo de la anemia en pacientes con hemorragia digestiva.

Despite high prevalence of iron deficiency anemia (IDA) in patients with acute or chronic gastrointestinal bleeding (GIB), IDA and iron deficiency (ID) are frequently untreated. Reasons may be misconceptions about the impact and diagnosis of IDA and the efficacy of new treatments. Addressing these misconceptions, this article summarizes current evidence for better understanding and management of GIB-associated IDA. Despite only few controlled studies evaluated the efficacy of iron treatment in patients with GIB, there is consistent evidence suggesting that: (a) IDA should be diligently investigated, (b) effective treatment of ID/IDA improves outcomes such as health-related quality of life and can avoid severe cardiovascular consequences, and (c) intravenous iron should be considered as well-tolerated treatment in this setting. Overall, the misconceptions and practices outlined in this article should be replaced with strategies that are more in line with current guidelines and best practice in GIB and other underlying conditions of ID/IDA.