Acute lower gastrointestinal bleeding (LGIB) is a common reason for hospitalization in the United States and is associated with significant utilization of hospital resources, as well as considerable morbidity and mortality. These revised guidelines implement the Grading of Recommendations, Assessment, Development, and Evaluation methodology to propose recommendations for the use of risk stratification tools, thresholds for red blood cell transfusion, reversal agents for patients on anticoagulants, diagnostic testing including colonoscopy and computed tomography angiography (CTA), endoscopic therapeutic options, and management of antithrombotic medications after hospital discharge. Important changes since the previous iteration of this guideline include recommendations for the use of risk stratification tools to identify patients with LGIB at low risk of a hospital-based intervention, the role for reversal agents in patients with life-threatening LGIB on vitamin K antagonists and direct oral anticoagulants, the increasing role for CTA in patients with severe LGIB, and the management of patients who have a positive CTA. We recommend that most patients requiring inpatient colonoscopy undergo a nonurgent colonoscopy because performing an urgent colonoscopy within 24 hours of presentation has not been shown to improve important clinical outcomes such as rebleeding. Finally, we provide updated recommendations regarding resumption of antiplatelet and anticoagulant medications after cessation of LGIB.
Publications
2023
BACKGROUND AIMS: Preventative care plays an important role in maintaining health in patients with inflammatory bowel disease (IBD). We aimed to assess the overall quality, strength, and transparency of conflicts among guidelines on preventative care in IBD.
METHODS: A systematic literature search was performed in multiple databases to identify all guidelines pertaining to preventative care in IBD in April 2021. All guidelines were reviewed for the transparency of conflicts of interest and funding, recommendation quality and strength, external guideline review, patient voice inclusion, and plan for update-as per Institute of Medicine standards. In addition, recommendations and their quality were compared between societies.
RESULTS: Fifteen distinct societies and a total of 89 recommendations were included. Not all guidelines provided recommendations on the key aspects of preventative care in IBD-such as vaccinations, cancer prevention, stress reduction, and diet/exercise. Sixty-seven percent of guidelines reported on conflicts of interest, 20% underwent external review, and 27% included patient representation. In all, 6.7%, 21.3%, and 71.9% of recommendations were based on high, moderate, and low-quality evidence, respectively. Twenty-seven percent, 23.6%, and 49.4% of recommendations were strong, weak/conditional, and did not provide a strength, respectively. The proportion of high-quality evidence ( P =0.28) and strong recommendations ( P =0.41) did not significantly differ across societies.
CONCLUSIONS: Many guidelines do not provide recommendations on key aspects of preventative care in IBD. As over 70% of recommendations are based on low-quality evidence, further studies on preventative care in IBD are warranted to improve the overall quality of evidence.
Gut-directed hypnotherapy (GDH) is a highly effective brain-gut behavioral therapy which is recommended in international guidelines for the treatment of irritable bowel syndrome (IBS). There is increasing recognition of the value of GDH as part of integrated care alongside medical and dietary approaches. This has led to recent innovations to widen access to GDH to meet the increasing demand. Recent advances include streamlined courses of individualized GDH, group therapy, and remote delivery. In this issue of Neurogastroenterology and Motility, Peters et al. retrospectively report outcomes of smartphone app-delivered GDH in a population with self-reported IBS. While adherence was low, those that completed smart phone-delivered GDH-achieved symptom benefit. This mini-review summarizes the current evidence-base for available modalities of GDH and discusses the current and future utility and development of mobile health applications in the digital therapeutics' era.
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Loss of estrogen, as occurs with normal aging, leads to increased inflammation, pathologic angiogenesis, impaired mitochondrial function, and microvascular disease. While the influence of estrogens on purinergic pathways is largely unknown, extracellular adenosine, generated at high levels by CD39 and CD73, is known to be anti-inflammatory in the vasculature. To further define the cellular mechanisms necessary for vascular protection, we investigated how estrogen modulates hypoxic-adenosinergic vascular signaling responses and angiogenesis. Expression of estrogen receptors, purinergic mediators inclusive of adenosine, adenosine deaminase (ADA), and ATP were measured in human endothelial cells. Standard tube formation and wound healing assays were performed to assess angiogenesis in vitro. The impacts on purinergic responses in vivo were modeled using cardiac tissue from ovariectomized mice. CD39 and estrogen receptor alpha (ERα) levels were markedly increased in presence of estradiol (E2). Suppression of ERα resulted in decreased CD39 expression. Expression of ENT1 was decreased in an ER-dependent manner. Extracellular ATP and ADA activity levels decreased following E2 exposure while levels of adenosine increased. Phosphorylation of ERK1/2 increased following E2 treatment and was attenuated by blocking adenosine receptor (AR) and ER activity. Estradiol boosted angiogenesis, while inhibition of estrogen decreased tube formation in vitro. Expression of CD39 and phospho-ERK1/2 decreased in cardiac tissues from ovariectomized mice, whereas ENT1 expression increased with expected decreases in blood adenosine levels. Estradiol-induced upregulation of CD39 substantially increases adenosine availability, while augmenting vascular protective signaling responses. Control of CD39 by ERα follows on transcriptional regulation. These data suggest novel therapeutic avenues to explore in the amelioration of post-menopausal cardiovascular disease, by modulation of adenosinergic mechanisms.
BACKGROUND: Hyperemesis gravidarum is the most severe form of nausea and vomiting of pregnancy, potentially affecting both maternal and pregnancy health. Hyperemesis gravidarum often results in emergency department visits, although the exact frequency and costs associated with these visits have not been well studied.
OBJECTIVE: This study aimed to analyze the trends in hyperemesis gravidarum emergency department visits, inpatient admissions, and the associated costs between 2006 and 2014.
STUDY DESIGN: Patients were identified from the 2006 and 2014 Nationwide Emergency Department Sample database files using International Classification of Diseases, Ninth Revision diagnosis codes. Patients with a primary diagnosis of hyperemesis gravidarum, nausea and vomiting of pregnancy, and all nondelivery pregnancy-related diagnoses (all antepartum visits) were identified. All groups were analyzed; trends in demographics, number of emergency department visits, and visit costs were compared. Costs were inflation-adjusted to 2021 US dollars.
RESULTS: Emergency department visits for hyperemesis gravidarum increased by 28% from 2006 to 2014; however, the proportion of those who were subsequently admitted to the hospital decreased. The average cost of an emergency department visit for hyperemesis gravidarum increased by 65% ($2156 to $3549), as opposed to an increase of 60% for all antepartum visits ($2218 to $3543). The aggregate cost for all hyperemesis gravidarum visits increased by 110% ($383,681,346 to $806,696,513) from 2006 to 2014, which was similar to the increase observed for all antepartum emergency department visits.
CONCLUSION: From 2006 to 2014, emergency department visits for hyperemesis gravidarum increased by 28%, with associated costs increasing by 110%, whereas the number of admissions from the emergency department for hyperemesis gravidarum decreased by 42%.
INTRODUCTION: Unspecified functional bowel disorder (FBD-U) is a Rome IV diagnosis of exclusion and occurs when patients report bowel symptoms but do not meet the criteria for other functional bowel disorders (FBD; irritable bowel syndrome [IBS], functional constipation [FC], functional diarrhea [FDr], or functional bloating). Previous research suggests that FBD-U is as/more common than IBS.
METHODS: One thousand five hundred one patients at a single-center tertiary care center completed an electronic survey. Study questionnaires included Rome IV Diagnostic Questionnaires, anxiety, depression, sleep, health care utilization, and bowel symptom severity measures.
RESULTS: Eight hundred thirteen patients met Rome IV criteria for a FBD and 194 patients (13.1%) met criteria for FBD-U, representing the second most common FBD after IBS. Severity of abdominal pain, constipation, and diarrhea were lower in FBD-U compared with other FBD, whereas health care utilization was similar among the groups. Scores on measures of anxiety, depression, and sleep disturbances were similar in FBD-U compared with FC and FDr but were less severe than IBS. Between 25% and 50% of patients with FBD-U did not meet Rome IV criteria for other FBD due to timing of onset of the target symptom (e.g., constipation for FC, diarrhea for FDr, and abdominal pain for IBS).
DISCUSSION: FBD-U, by Rome IV criteria, is highly prevalent in clinical settings. These patients are not represented in mechanistic studies or clinical trials for not having met Rome IV criteria for other FBD. Making future Rome criteria less stringent would minimize the number fulfilling criteria for FBD-U and maximize the true representation of FBD in clinical trials.
BACKGROUND: Therapeutic drug monitoring (TDM) is a decision-making tool for optimizing the use of certain therapies. In this article, the authors review the role of proactive TDM of biological agents in patients with inflammatory bowel disease (IBD) and other immune-mediated inflammatory diseases (IMID). They also discuss the future of TDM as a component of personalized medicine from the clinical laboratory perspective.
METHODS: This narrative review originated from proceedings of the fifth biannual Challenges in Therapeutic Drug Monitoring seminar and was supplemented by additional literature identified at various stages of critical review.
RESULTS: Proactive TDM aims to achieve adequate concentrations of biological drugs, such that patients attain and maintain an optimal treatment response. Proactive TDM may also have a role in de-escalating anti-tumor necrosis factor therapy in patients in clinical remission and in optimizing infliximab monotherapy as an alternative to combination therapy with an immunomodulator. A major proactive TDM application is in pediatric patients with IBD. Achieving mucosal healing in children with IBD requires that infliximab or adalimumab concentrations are monitored early during induction therapy, with dose modifications guided by the timing (week) of measurement. Recent innovations in biological therapy include international standards for infliximab and adalimumab for the global harmonization of bioactivity and monotest devices with an accuracy equivalent to that of conventional enzyme-linked immunosorbent assays and quicker turnaround times.
CONCLUSIONS: Despite several knowledge gaps regarding proactive TDM of anti-tumor necrosis factor therapy in patients with IMID, growing evidence suggests that it is associated with better outcomes than empiric optimization and/or reactive TDM in IBD. Enhanced pharmacokinetic modeling to predict drug exposure and patient genotyping for the precise application of proactive TDM are considered key elements to optimize biological therapy in the future.