William Hirsch

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.

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.

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.

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

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.

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

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).

Clinical and manometric characteristics of women with paradoxical puborectalis syndrome

Background & Aims Fecal urgency is a common symptom among patients with gastrointestinal disorders, but can also occur in healthy individuals with normal bowel habits. There have been few studies of fecal urgency in the general population. We performed a cross‐sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) to analyze the prevalence of and risk factors for this symptom. Methods We analyzed data from 4676 persons who completed the Bowel Health Questionnaire from the NHANES, from 2009 through 2010. The NHANES sampled a nationally representative group of adults in the United States and provides information on demographics, medical comorbidities, and dietary habits of survey participants. The Bowel Health Questionnaire provided additional information about bowel symptoms such as urgency, incontinence, constipation, and diarrhea. We identified individuals with fecal urgency and calculated differences in fecal urgency among subgroups using chi‐squared analysis. We used logistic regression to identify factors associated with urgency. Results In our study population, the prevalence of fecal urgency was 3.3%; 29.5% of individuals with fecal urgency had diarrhea. The prevalence of fecal urgency was significantly higher in individuals who had diarrhea (14.8%) than in individuals without diarrhea (3.1%). Older age, female sex, poverty, urinary urge incontinence, diarrhea, and increased stool frequency were all associated with fecal urgency on multivariable analysis. Decreased fiber intake and increased carbohydrate intake were associated with urgency among individuals with diarrhea. Conclusions In an analysis of data from 4676 individuals who completed a Bowel Health Questionnaire from the NHANES, we found a significantly higher proportion of individuals with diarrhea to have fecal urgency. However, most individuals with fecal urgency do not have diarrhea. Factors associated with fecal urgency vary among individuals with and without diarrhea.

Sleep Disturbances Are Commonly Reported Among Patients Presenting to a Gastroenterology Clinic

Despite advances in treatment, patients with inflammatory bowel disease (IBD) frequently require emergency department (ED) visits and hospitalisations.

Factors Associated With Response to Placebo in Patients With Irritable Bowel Syndrome and Constipation

Background A subset of patients with functional defecation disorders have predominance of the puborectalis muscle (PRM) on three-dimensional high definition anorectal manometry (HDARM), known as paradoxical puborectalis syndrome (PPS). The aim of this study was to assess clinical and manometric differences between patients with and without PPS. Methods A total of 227 women with functional defecation disorders undergoing HDARM between December 2012 and October 2016 at a single center were included in this study. All completed the Rome III constipation module and Pelvic Floor Distress Inventory 20 (PFDI-20). Results Eighty-seven out of 227 women had a 3D pressure topographic profile consistent with PPS. They had higher mean PDFI-20 scores for straining and incomplete evacuation symptoms than those without PPS. In addition, they demonstrated higher mean resting anal pressure, a more negative mean anorectal pressure differential, and a greater proportion with prolonged balloon expulsion test. These findings were more pronounced in a subgroup of 58 PPS patients with a distinct pattern of both posterior and posterolateral wall indentation. Conclusion Among female patients with functional defecation disorders, those with PPS demonstrated clinical and manometric differences compared to those without PPS. These differences may be driven by predominant posterolateral wall indentation in a subgroup of PPS patients.