Karen Lasch

Irritable bowel syndrome: Methods, mechanisms, and pathophysiology. the confluence of increased permeability, inflammation, and pain in irritable bowel syndrome

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal ailments among those seeking health care for gastrointestinal disorders. Despite its prevalence, IBS pathophysiology is still not completely understood. Continued elucidation of IBS etiological mechanisms will lead to a greater appreciation of possible therapeutic targets. In the past decade, there has been increasing focus on the possible connection between increased intestinal mucosal permeability, inflammation, and visceral hypersensitivity. Increased permeability in subsets of IBS patients has been observed and the possible mechanisms underlying this defect are just beginning to be understood. The objectives of this review are to summarize the role of the healthy intestinal epithelium as a barrier between the lumen and the rest of the body with a focus on tight junctions; to examine the lines of evidence that suggest that different triggers lead to increased intestinal mucosal permeability and disruption of tight junctions in IBS patients; and to explore how this increased permeability may elicit immune responses that affect afferent nerves, resulting in the pain associated with IBS.

Vedolizumab exposure in pregnancy: outcomes from clinical studies in inflammatory bowel disease

Vedolizumab is a gut‐selective immunoglobulin G1 monoclonal antibody to α4β7 integrin for the treatment of Crohns disease (CD) and ulcerative colitis (UC). Prospective clinical studies of vedolizumab in pregnancy have not been conducted; therefore, existing safety data of vedolizumab in pregnancy were examined.

A Gap in Our Understanding: Chronic Constipation and Its Comorbid Conditions

Constipation is one of the most common digestive disorders in the United States; however, the association of this condition with related comorbidities, both gastrointestinal and extraintestinal, is poorly documented. Here, we have reviewed the association of constipation with specific comorbidities. The data suggest that there are considerable clinical consequences associated with constipation. Ultimately, realization of the disease risks associated with chronic constipation may provide the impetus needed to direct new research, and shift attention on the part of patients and practitioners to methods for preventing significant and potentially costly comorbid medical problems.

Risk of developing colorectal cancer and benign colorectal neoplasm in patients with chronic constipation

Chronic constipation (CC) is a highly prevalent health problem, potentially associated with increased risk of colorectal cancer (CRCancer).

Vedolizumab as Induction and Maintenance Therapy for Crohn's Disease in Patients Naïve to or Who Have Failed Tumor Necrosis Factor Antagonist Therapy.

Background: Vedolizumab is a gut-selective &agr;4&bgr;7 integrin antagonist for the treatment of moderately to severely active Crohns disease (CD). Aims of this study were to characterize the efficacy and safety of vedolizumab induction and maintenance therapy in patients who were naïve to tumor necrosis factor-alpha (TNF-&agr;) antagonist therapy (TNF-naïve) or who had discontinued TNF-&agr; antagonist therapy because of inadequate response (i.e., primary nonresponse), loss of response, or intolerance (collectively classified as the TNF-failure population). Methods: Post hoc analyses of the efficacy data for 516 TNF-naïve and 960 TNF-failure patients from the GEMINI 2 and GEMINI 3 trials were evaluated at weeks 6, 10, and 52 and included clinical remission (CD Activity Index [CDAI] score ⩽150), enhanced clinical response (≥100-point decrease from baseline in CDAI score), durable clinical remission (remission at ≥80% of visits), and corticosteroid-free remission. Adverse events were summarized for the TNF-naïve and TNF-failure subgroups by treatment received. Results: Among patients who responded to vedolizumab induction at week 6, 48.9% of TNF-naïve and 27.7% of TNF-failure patients were in remission with vedolizumab at week 52 (versus 26.8% and 12.8% with placebo). Clinical efficacy was similar between the different types of TNF-&agr; antagonist failure or the number of prior TNF-&agr; antagonists failed. Safety profiles were similar in both subpopulations. Conclusions: Vedolizumab had increased efficacy over placebo in CD patients irrespective of TNF-&agr; antagonist treatment history. Overall, rates of response and remission were numerically higher in patients receiving vedolizumab as a first biologic than in patients who had experienced TNF failure.

Seasonal patterns of abdominal pain consultations among adults and children.

Background and Aim: Consultations for chronic abdominal pain are frequent in adults and children. A seasonal pattern of abdominal pain consultations with winter predominance was shown in previous pediatric studies; however, no studies have investigated whether such a pattern exists in adult patients. Understanding the differences in seasonal patterns of abdominal pain consultations among adults and children may indicate that either different mechanisms exist for common chronic pain conditions or triggering factors may vary by age. The aim of the study was to investigate whether a seasonal variation in abdominal pain consultation patterns exists among adults and children. Methods: The number of outpatient consultations among children (5–17 years) and adults (18 years or older) with a diagnosis of abdominal pain of nonspecified origin (International Classification of Diseases-9 code 789.0) from May 2000 to December 2008 was identified in an administrative claims database. The primary outcome measure was the rate of abdominal pain consultations (total number of abdominal pain consultations/total number of distinct patients by month × 1000) by season in children and adults. Seasons were defined as follows: winter (December–February), spring (March–May), summer (June–August), and fall (September–November). A trend test was conducted to determine the degree of linearity in the patterns between the 2 groups. Among children, subanalyses by age 5 to 11 years and 12 to 17 years and sex were conducted. Results: A total of 172.4 million distinct patients (13.4% children, 87.6% adults) were identified in the database between May 2000 and December 2008. During the same time period, 15.6 million patient consultations for abdominal pain were identified (10.1% children, 89.9% adults). Children demonstrated a seasonal pattern in abdominal pain consultations, which best fit a quadratic regression curve, with consultations less common during the summer months. Abdominal pain consultations in adults were linear with no seasonal predominance. The trend in seasonal variation of abdominal pain consultations among children stratified by age and sex remained consistent with the overall child population. Conclusions: Abdominal pain consultations in children are less common during summer months, whereas no evidence of seasonal pattern of consultation was found in adults. Factors involved in the pathogenesis of abdominal pain in adults and children may differ.

Effects of vedolizumab on health-related quality of life in patients with ulcerative colitis: results from the randomised GEMINI 1 trial

Health‐related quality of life (HRQL) is often diminished in patients with ulcerative colitis.

Prevalence and risk of developing comorbid conditions in patients with chronic constipation

Abstract Objective: To estimate the prevalence of gastrointestinal (GI) and non-GI comorbidities and the risk of incident comorbidities among patients with and without chronic constipation (CC). Research design and methods: Adults with CC were identified from a large retrospective US claims database. Each CC patient was matched 1:3 to CC-free patients by birth year, sex, and region of residence. Main outcome measures: Prevalence of GI and non-GI comorbidities was measured over a 1-year period. Relative risk of new comorbidities was also estimated among patients who were free of the studied comorbidity prior to the index date. Results: Mean age was 61.9 years; 33.3% of patients were male. The 1-year prevalence of GI comorbidities was significantly higher in CC (N = 28,854) vs. CC-free (N = 86,562) patients (all p < 0.05). The risk of developing new GI conditions was also significantly higher in CC patients for all studied conditions except ulcerative colitis: megacolon (hazard ratio [95% confidence interval] HR [CI] = 11.96 [8.16–17.53]), intestinal impaction (10.56 [9.22–12.10]), volvulus (7.12 [5.42–9.35]), other specified functional intestinal disorders (6.67 [5.57–8.00]), and other unspecified functional disorders of intestine (4.60 [3.61–5.87]). Similarly, 1-year prevalence of non-GI comorbidities was higher in CC patients, as was the risk of developing new conditions: depression and mood disorder (HR [CI] = 1.84 [1.77–1.90]), neurological disorders (1.68 [1.62–1.74]), iron deficiency anemia (1.52 [1.47–1.57]), hypothyroidism (1.40 [1.34–1.46]), and peripheral vascular disorders (1.40 [1.34–1.46]). Limitations: An algorithm was used to define CC as there is no specific diagnosis code to identify CC. Conclusions: CC patients had significantly higher prevalence and were at increased risk of developing new GI and non-GI comorbidities than age-, gender- and region-matched CC-free patients. Future research is warranted to better understand these associations.

Management of Inflammatory Bowel Disease in the Elderly Patient: Challenges and Opportunities

Abstract: The population of older patients with inflammatory bowel disease (IBD) continues to grow, partly reflecting the aging global population in general. The debilitating effects of IBD compound age-related decrements in health and functional capacity, and make the medical management of older patients with Crohns disease and ulcerative colitis distinctly challenging to clinicians. Here, we review the recent literature describing the pharmacologic management of IBD in this population, with focus on the safety, tolerability, and efficacy of common treatment options, such as steroids, immunomodulators, tumor necrosis factor–&agr; antagonists, and integrin antagonists; surgical interventions in older patients are also discussed. Few studies have systematically and prospectively evaluated the clinical challenges in the medical management of IBD in this patient population, leaving a limited evidence base to which clinicians can turn to for guidance. Treatment patterns may thus be suboptimal. For example, prolonged steroid use in the elderly was found to be common, causing significant morbidity from side effects in a particularly vulnerable population. Finally, within the context of a limited evidence base, we discuss common treatment scenarios to define the parameters within which physicians can individualize care for older patients with IBD. Overall, older patients with IBD are at higher risk of adverse events and less treatment responsiveness compared with younger patients, underscoring the need for future studies to fully characterize appropriate treatment courses for this population.

Optimizing Selection of Biologics in Inflammatory Bowel Disease: Development of an Online Patient Decision Aid Using Conjoint Analysis

Objectives:Recent drug approvals have increased the availability of biologic therapies for inflammatory bowel disease (IBD), making it difficult for patients with ulcerative colitis (UC) and Crohn’s disease (CD) to navigate treatment options. Here we developed a conjoint analysis to examine patient decision-making surrounding biologic medicines for IBD. We used the results to create an online patient decision aid that generates a unique “preferences report” for each patient to assist with shared decision-making with their provider.Methods:We administered an adaptive choice-based conjoint survey to IBD patients that quantifies the relative importance of biologic attributes (e.g., efficacy, side effect profile, mode of administration, and mechanism of action) in decision making. The conjoint software determined individual patient preferences by calculating part-worth utilities for each attribute. We conducted regression analyses to determine if demographic and disease characteristics (e.g., type of IBD and severity) predicted how patients made decisions.Results:640 patients completed the survey (UC=304; CD=336). In regression analyses, demographics and IBD characteristics did not predict individual patient preferences; the main exception was IBD type. When compared to UC, CD patients were more likely to report side effect profile as most important (odds ratio (OR) 1.63, 95% confidence interval (CI) 1.16–2.30). Conversely, those with UC were more likely to value therapeutic efficacy (OR 1.41, 95% CI 1.01–2.00).Conclusions:Biologic decision-making is highly personalized; demographic and disease characteristics poorly predict individual preferences, indicating that IBD patients are unique and difficult to statistically categorize. The online decision tool resulting from this study (www.ibdandme.org) may be used by patients to support shared decision-making and optimize personalized biologic selection with their provider.