Judy Nee

Open-label versus double-blind placebo treatment in irritable bowel syndrome: study protocol for a randomized controlled trial

BackgroundPlacebo medications, by definition, are composed of inactive ingredients that have no physiological effect on symptoms. Nonetheless, administration of placebo in randomized controlled trials (RCTs) and in clinical settings has been demonstrated to have significant impact on many physical and psychological complaints. Until recently, conventional wisdom has suggested that patients must believe that placebo pills actually contain (or, at least, might possibly contain) active medication in order to elicit a response to placebo. However, several recent RCTs, including patients with irritable bowel syndrome (IBS), chronic low back pain, and episodic migraine, have demonstrated that individuals receiving open-label placebo (OLP) can still experience symptomatic improvement and benefit from honestly described placebo treatment.Methods and designThis paper describes an innovative multidisciplinary trial design (n = 280) that attempts to replicate and expand upon an earlier IBS OLP study. The current study will compare OLP to double-blind placebo (DBP) administration which is made possible by including a nested, double-blind RCT comparing DBP and peppermint oil. The study also examines possible genetic and psychological predictors of OLP and seeks to better understand participants’ experiences with OLP and DBP through a series of extensive interviews with a randomly selected subgroup.DiscussionOLP treatment is a novel strategy for ethically harnessing placebo effects. It has potential to re-frame theories of placebo and to influence how physicians can optimize watch-and-wait strategies for common, subjective symptoms. The current study aims to dramatically expand what we know about OLP by comparing, for the first time, OLP and DBP administration. Adopting a unique, multidisciplinary approach, the study also explores genetic, psychological and experiential dimensions of OLP. The paper ends with an extensive discussion of the “culture” of the trial as well as potential mechanisms of OLP and ethical implications.Trial registrationClinicalTrials.gov, identifier: NCT02802241. Registered on 14 June 2016.

Optimizing the Care and Health of Women with Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) including both ulcerative colitis and Crohns disease is increasing worldwide. Although diagnosis is equally found in men and women, the chronicity of IBD poses a unique impact on the milestones of a womans life. As the gastroenterologist becomes increasingly important in the health maintenance of patients with IBD, this review stresses the unique gender issues in women with IBD related to menstruation, cervical cancer, sexual health, contraception, and menopause that may affect the course of disease, treatment decisions, and quality of life.

Characterizing Normal Bowel Frequency and Consistency in a Representative Sample of Adults in the United States (NHANES)

Objectives:Our current understanding of normal bowel patterns in the United States (US) is limited. Available studies have included individuals with both normal and abnormal bowel patterns, making it difficult to characterize normal bowel patterns in the US. The current study aims to (1) examine frequency and consistency in individuals with self-reported normal bowel habits and (2) determine demographic factors associated with self-reported normalcy.Methods:This study used data from adult participants who completed bowel health questions as part of the National Health and Nutrition Examination Survey (NHANES) in 2009–2010 and who reported normal bowel patterns (N=4,775). Data regarding self-perceived bowel health; stool frequency; stool consistency (using the Bristol Stool Form Scale (BSFS)); and demographic factors were analyzed.Results:95.9% of the sample reported between 3 and 21 BMs per week. Among men, 90% reported a BSFS between 3 and 5, while for women it was 2–6. After controlling for age, the following demographic variables were associated with normalcy: male sex, higher education, higher income, <2 daily medications, and high daily fiber intake. Hispanic ethnicity was significantly associated with abnormal self-reported bowel habits.Conclusions:This is the first study to evaluate normal bowel frequency and consistency in a representative sample of adults in the US. The current findings bolster the common “3 and 3” metric of normal frequency (3 BMs/day to 3 BMs/week) while also suggesting different criteria for normal consistency for men and women. Finally, this study provides novel information about demographic factors associated with normal frequency and consistency.

Current and emerging drug options in the treatment of diarrhea predominant irritable bowel syndrome

Introduction: Irritable bowel syndrome diarrhea predominant (IBS-D) is a highly prevalent GI disease, affecting nearly a third of all patients diagnosed with irritable bowel syndrome. Current treatment options are limited. Areas covered: This review discusses the pharmacotherapeutic options for IBS-D including currently used medications, the two newly FDA approved medications, as well as emerging therapies with potential benefit in IBS-D. Particular emphasis is placed on rifaximin and eluxadoline and their possible use in IBS-D. Expert Opinion: Current pharmacological treatment of IBS-D includes loperamide, bile acid sequestrants, antispasmodics, tricyclic antidepressants, alosetron, eluxadoline and rifaximin. The latter two treatments have significantly added to the pharmacotherapeutic options for patients suffering from IBS-D.

Emergency Department Burden of Diverticulitis in the USA, 2006–2013

GoalsThe aim of this study was to analyze recent trends in emergency department (ED) visits for diverticulitis between 2006 and 2013.BackgroundAcute diverticulitis is a serious medical condition that frequently leads to ED visits, hospitalizations, and surgeries resulting in a significant health care burden.MethodsData were obtained from the National Emergency Department Sample (NEDS) records in which diverticulitis (ICD-9-CM codes 562.11 and 562.13) was the primary diagnosis in the ED between 2006 and 2013. The NEDS collects data from more than 25 million visits in over 950 hospital emergency departments and is weighted to provide national estimates. Our findings reflected patient and hospital characteristics such as demographics, geographical region, and total charges for ED and inpatient stays.ResultsBetween 2006 and 2013, the rate of diverticulitis-related ED visits increased by 26.8% from 89.8 to 113.9 visits per 100,000 population. The aggregate national cost of diverticulitis-related ED visits increased by 105%, from approximately

Efficacy of Treatments for Opioid-Induced Constipation: Systematic Review and Meta-analysis

822 million in 2006 to over

Gender differences in chronic constipation on anorectal motility

1.6 billion in 2013. Cost data were adjusted for inflation and reported in 2015 dollars. The percentage of individuals admitted to the same hospital from the ED decreased from 58.0 to 47.1% from 2006 to 2013, respectively, while the rate of bowel surgeries per 100,000 ED visits for diverticulitis decreased by 33.7% from 2006 to 2013.ConclusionsThe number of ED visits due to diverticulitis and associated costs continued to rise between 2006 and 2013, while the rate of bowel surgeries and inpatient admissions through the ED for diverticulitis decreased.

Novel Therapies in IBS-D Treatment

Background & Aims Opioid‐induced constipation (OIC) is a common problem in patients on chronic opioid therapy for cancer‐related and non–cancer‐related pain. Approved treatments for OIC are methylnaltrexone, naloxone, naloxegol, alvimopan, naldemedine, and lubiprostone. Since a meta‐analysis performed in 2014, 2 new agents have been approved by the Food and Drug Administration for treatment of OIC (naloxegol and naldemedine). Methods We conducted a search of the medical literature following the protocol outlined in the Cochrane Handbook for systematic review. We searched MEDLINE, EMBASE, EMBASE Classic, Web of Science, and the Cochrane Central Register of Controlled Trials until March 2017 to identify randomized controlled trials of peripheral &mgr;‐opioid–receptor antagonists (methylnaltrexone, naloxone, naloxegol, alvimopan, axelopran, or naldemedine), lubiprostone, or prucalopride. Response to therapy was extracted in a dichotomous assessment as an overall response to therapy. The effect of pharmacologic therapies was pooled and reported as a relative risk (RR) of failure to respond to the treatment drug, with 95% CIs. Results We included 27 placebo‐controlled trials in our meta‐analysis (23 trials evaluated &mgr;‐opioid–receptor antagonists, 3 trials evaluated lubiprostone, and 1 trial evaluated prucalopride). In these trials, 5390 patients received a drug and 3491 received a placebo. Overall, &mgr;‐opioid–receptor antagonists, lubiprostone, and prucalopride were superior to placebo for the treatment of OIC, with a RR of failure to respond to therapy of 0.70 (95% CI, 0.64–0.75) and an overall number needed to treat of 5 (95% CI, 4–7). When restricted to only Food and Drug Administration–approved medications for OIC, the RR of failure to respond to therapy was 0.69 (95% CI, 0.62‐0.77), with a number needed to treat of 5 (95% CI, 4–7). Sensitivity analyses and meta‐regression performed to account for heterogeneity showed that treatment was more likely to be effective in study populations taking higher doses of opiates at baseline or refractory to laxatives. Study duration and prespecified primary outcome did not affect the RR of failure. Participants who received &mgr;‐opioid–receptor antagonists were significantly more likely to have diarrhea, abdominal pain, nausea, or vomiting than patients who received placebo. Conclusions In a systematic review and meta‐analysis, we found &mgr;‐opioid–receptor antagonists to be safe and effective for the treatment of OIC. Prescription‐strength laxatives (prucalopride, lubiprostone) are slightly better than placebo in reducing OIC.

Risk Factors for Fecal Urgency Among Individuals With and Without Diarrhea, Based on Data From the National Health and Nutrition Examination Survey

The epidemiology of chronic constipation (CC) skews toward female predominance, yet men make up an important component of those suffering from CC. We sought to determine whether there are sex‐specific differences in symptoms and physiologic parameters on anorectal manometry (ARM).

Emergency department utilisation for inflammatory bowel disease in the United States from 2006 to 2014

Opinion statementIrritable bowel syndrome (IBS) is a common gastrointestinal disease characterized by abdominal pain and change in bowel habits. IBS diarrhea predominant (IBS-D), which is arguably the most common subset of IBS, is also associated with rectal urgency, increased frequency, abdominal bloating, and loose to watery stools. Current treatments for diarrhea include mu-opioid agonists (i.e., loperamide, lomotil) and bile acid sequestrants (i.e., cholestyramine) while treatments for abdominal pain include antispasmodics (i.e., hyoscyamine, dicyclomine) and tricyclic antidepressants (i.e., amitriptyline). There are currently 3 FDA-approved treatments for IBS-D, which have been shown to improve both abdominal pain and diarrhea. Alosetron was initially approved by FDA 2000; however, its use is now limited to women with severe IBS-D symptoms refractory to other treatment. Eluxadoline, a mixed mu-opioid agonist, and rifaximin, a broad spectrum gut specific antibiotic, were both FDA approved in 2015. Eluxadoline has been shown to relieve abdominal pain and stool consistency in appropriate candidates. While large trials already showed the efficacy of rifaximin in treating non-constipated IBS for bloating, stool consistency, and abdominal pain, the recent TARGET 3 trial demonstrates that retreatment is also effective. While these new treatments significantly expand options for patients suffering from IBS-D, there is likely to remain a need for additional safe and effective therapies.