Macrophage activation syndrome with acute hepatitis in a patient with adult-onset immunodeficiency with anti-interferon gamma antibodies: a case report.

BACKGROUND: Macrophage activation syndrome is a rare disorder leading to unregulated immune activity manifesting with nonspecific constitutional symptoms, laboratory abnormalities, and multiorgan involvement. We report the case of a patient who presented with acute hepatitis secondary to macrophage activation syndrome diagnosed by liver biopsy and successfully treated with intravenous immune globulin, anakinra, and rituximab. CASE PRESENTATION: A 42-year-old Laotian woman with adult-onset immunodeficiency with anti-interferon gamma antibodies presented with a fever, headache, generalized myalgia, dark urine, and reduced appetite in the setting of family members at home with similar symptoms. Her laboratory workup was notable for evidence of acute hepatitis without acute liver failure. After an unrevealing comprehensive infectious and noninvasive rheumatologic workup was completed, a liver biopsy was performed ultimately revealing the diagnosis of macrophage activation syndrome. She was successfully treated with intravenous immune globulin, anakinra, and rituximab. CONCLUSION: This case highlights the importance of maintaining macrophage activation syndrome on the differential of a patient with acute hepatitis of unknown etiology in the correct clinical context and the value of a liver biopsy in making a diagnosis when noninvasive testing is unrevealing.

Peppermint Oil Treatment for Irritable Bowel Syndrome: A Randomized Placebo-Controlled Trial.

INTRODUCTION: Peppermint oil is often used to treat irritable bowel syndrome (IBS); however, the overall quality of previous studies is low, and findings have been heterogeneous. This study aimed to compare the effects of peppermint oil vs placebo in relieving IBS symptoms. METHODS: In a 6-week, randomized, double-blind, placebo-controlled trial at a single academic center in the United States, individuals diagnosed with IBS (Rome IV criteria), with moderate to severe symptoms based on the IBS Severity Scoring System (IBS-SSS score ≥175), were randomized to enteric-coated peppermint oil 180 mg 3 times daily vs placebo in a 1:2 ratio. The primary outcome was mean change in IBS-SSS scores from baseline to 6-week endpoint. RESULTS: A modified intent-to-treat analysis revealed that there were substantial mean improvements from baseline to 6-week endpoint in the main outcome measure (IBS-SSS) for both peppermint oil (90.8, SD = 75.3) and placebo (100.3, SD = 99.6). Although the peppermint oil group reported numerically lower improvement than the placebo group, the effect size was small (d = -0.11), and the difference between the groups was not statistically significant (P = 0.97). Similarly, both groups reported substantial improvements on the secondary endpoints; but again, there were no statistically significant differences between the groups on any of the secondary measures. Sensitivity analyses using multiple imputation to replace missing data produced similar results and revealed no significant differences between peppermint oil and placebo on any outcome measure. DISCUSSION: Peppermint oil and placebo both showed clinically meaningful improvement in IBS symptoms. However, there were no significant differences between the groups. Further large, rigorous trials are needed to evaluate the role of peppermint oil for the treatment of IBS.

Open-label placebo vs double-blind placebo for irritable bowel syndrome: a randomized clinical trial.

ABSTRACT: It is commonly believed that blinding to treatment assignment is necessary for placebos to have an effect. However, placebos administered without concealment (ie, open-label placebos [OLPs]) have recently been shown to be effective in some conditions. This study had 2 objectives: first, to determine whether OLP treatment is superior to no-pill control (NPC) in irritable bowel syndrome (IBS) and, second, to compare the efficacy of OLP against double-blind placebo (DBP). In a 6-week, 3-arm, randomized clinical trial, participants were randomized in equal proportions to 3 arms: OLP, DBP, or NPC. Two hundred sixty-two adults (72.9% women), with a mean age of 42.0 (SD = 18.1) years, participated in the primary study. The mean improvement on the IBS Severity Scoring System from baseline to the 6-week end point was significantly greater in OLP compared with that in NPC (90.6 vs 52.3, P = 0.038). Open-label placebo and DBP did not differ significantly on IBS Severity Scoring System improvement (100.3 vs 90.6, P = 0.485). Standardized effect sizes were moderate for OLP vs NPC (d = 0.43) and small for OLP vs DBP (d = 0.10). Participants treated with OLP reported clinically meaningful improvements in IBS symptoms that were significantly greater than those on NPC. Open-label placebo and DBP had similar effects that did not differ significantly, suggesting that blinding may not be necessary for placebos to be effective and that OLP could play a role in the management of patients with refractory IBS.

Fecal Urgency: Clinical and Manometric Characteristics in Patients With and Without Diarrhea.

BACKGROUND: Fecal urgency is classically associated with diarrhea, but is also common in individuals with normal bowel habits or constipation. Its etiology, particularly in non-diarrhea individuals, is unclear. METHODS: We examined data from 368 individuals with and without diarrhea who underwent three-dimensional high-resolution anorectal manometry and balloon expulsion test. All patients completed the Rome III constipation module and the pelvic floor distress inventory (PDFI-20) survey. Patients were considered to have fecal urgency if they reported being bothered "moderately" or "quite a bit" by it in the past 3 months. RESULTS: A total of 103 patients (28.0%) met our definition of fecal urgency. These patients were significantly more likely to meet criteria for irritable bowel syndrome and to report fecal incontinence, urinary incontinence, and diarrhea. Fecal urgency was associated with rectal hypersensitivity in those with diarrhea, but not in those without diarrhea. Fecal urgency was associated with urinary urge incontinence in those without diarrhea, but not those with diarrhea. CONCLUSIONS: In patients with diarrhea, fecal urgency is associated with rectal hypersensitivity, whereas in patients without diarrhea, fecal urgency is associated with urinary urge incontinence. This suggests that fecal urgency has different pathophysiological mechanisms in patients with different underlying bowel habits.

Cavernous-Carotid Fistula Presenting with Intracerebral Hemorrhage in the Absence of Ocular Symptoms.

BACKGROUND: Cavernous-carotid fistulas (CCFs) can present with a variety of symptoms depending on the anatomy of the fistula and its venous drainage. Patients most commonly present with scleral injection, pulsatile exophthalmos, and/or chemosis. CASE DESCRIPTION: We report a patient who presented with intraparenchymal hemorrhage in the absence of any of the commonly associated ocular symptoms and signs. After multiple imaging studies, the CCF was diagnosed and treated with endovascular embolization that resulted in complete occlusion of the fistula and reflux of embolysate into one of its connecting veins. CONCLUSIONS: The morphology of the venous drainage can lead to atypical hemorrhagic presentation, whereas dilatation of one of the tributary veins with cortical venous reflux should warn the interventionist the path the embolysate may follow. We provide our experience with this unique presentation and its treatment.

Emergency department visits for depression in the United States from 2006 to 2014.

BACKGROUND: Patients with depression frequently seek care in the emergency department (ED), especially in the context of suicidal ideation (SI) and self-harm (SH). However, the prevalence and trends in the United States (US) of ED visits for depression have not yet been characterized using a nationally representative sample. This study evaluates ED trends for depression in the US from 2006 to 2014. METHODS: Data was obtained from the Nationwide Emergency Department Sample (NEDS) in 2006 and 2014 using a primary ICD-9 diagnosis of depression or a primary diagnosis of suicidal ideation (SI) and a secondary diagnosis of depression. RESULTS: Between 2006 and 2014, there was a 25.9% increase in visits to the ED for depression, which was higher than the 14.8% increase in total ED visits during this time period. The mean inflation adjusted charges associated with depression-related ED visits increased by 107.7%, which was higher than the increase in mean charges for all ED visits in the same time period (40.47%). Visit rates were bimodally distributed with respect to age, with peaks in adolescence and middle age. Notably there was a 61.3% increase in ED visits for depression in individuals younger than 20 between 2006 and 2014. Over half of patients were admitted for inpatient care with a mean length of stay of 5.6 days in both years. Inpatient charges increased 71.8% between 2006 and 2014. CONCLUSIONS: ED visits for depression in the United States rose 25.9% between 2006 and 2014, which was higher than the 14.8% increase in total ED visits during this time period. Over half of ED depression visits were admitted to inpatient stay (mean 5.6 days both years).

Pelvic Floor Symptom Related Distress in Chronic Constipation Correlates With a Diagnosis of Irritable Bowel Syndrome With Constipation and Constipation Severity but Not Pelvic Floor Dyssynergia.

BACKGROUND/AIMS: Although symptoms related to the pelvic floor, such as pelvic organ prolapse (POP) and lower urinary tract symptoms (LUTS), are common in patients with chronic constipation (CC), its impact is not clear. Our aims were to investigate the following (1) compare pelvic floor symptom related dysfunction in irritable bowel syndrome with constipation (IBS-C) and functional constipation (FC), and (2) symptom correlation with findings on anorectal manometry (ARM) and balloon expulsion test. METHODS: This was a retrospective analysis of patients with CC undergoing ARM. IBS-C and FC were diagnosed by Rome III criteria. Pelvic Floor Distress Inventory (PFDI-20) was used to measure pelvic floor symptom distress. Constipation Severity Scale was used to assess constipation severity. RESULTS: A total of 107 patients underwent ARM (64 FC, 43 IBS-C). The overall PFDI-20 score in IBS-C was higher compared with FC patients (118.0 vs 79.2, P = 0.001). In those with IBS-C, POP, LUTS, and colorectal symptoms subscales were all higher compared with FC patients ( P ＜ 0.05 for each). On multivariable regression, IBS-C ( P = 0.001) and higher constipation severity ( P = 0.001) were both independently associated with higher PFDI scores. ARM parameters and abnormal balloon expulsion test did not correlate with PFDI scores. CONCLUSIONS: Compared with FC patients, those with IBS-C have significantly higher distress from pelvic floor specific symptoms including POP and LUTS. Higher abdominal pain among IBS-C patients did not entirely explain these findings. A diagnosis of IBS-C and higher constipation severity correlated with PFDI-20 scores, but dyssynergia did not.

Prevalence of Functional GI Diseases and Pelvic Floor Symptoms in Marfan Syndrome and Ehlers-Danlos Syndrome: A National Cohort Study.

BACKGROUND AND AIMS: Prior studies have shown a high prevalence of gastrointestinal (GI) symptoms, diagnoses of functional GI diseases (FGIDs), and pelvic floor symptoms associated with Ehlers-Danlos syndrome (EDS). It is unclear if Marfan syndrome (MFS), another common hereditary noninflammatory connective tissue disorder, is also associated these symptoms. This study evaluates the prevalence of and compares FGIDs and pelvic floor symptoms in a national cohort of EDS and MFS patients. METHODS: A questionnaire was sent to members of local and national MFS and EDS societies. The questionnaire evaluated the presence of GI and pelvic floor symptoms and diagnoses. The presence of FGIDs was confirmed using Rome III criteria. Quality of life was evaluated and scored with the CDC quality of life. KEY RESULTS: Overall, 3934 patients completed the questionnaire, from which 1804 reported that they had some form of EDS and 600 had MFS. In total, 93% of patients with EDS complained of GI symptoms and qualified for at least one FGID compared with 69.8% of patients with MFS. When comparing EDS prevalence of upper and lower GI symptoms as well as FGIDs, subjects with EDS reported significantly higher prevalence of Rome III FGIDs as compared with those with MFS. Irritable bowel syndrome (57.8% vs. 27.0%, P<0.001), functional dyspepsia (FD) (55.4% vs. 25.0%, P<0.001), postprandial distress (49.6% vs. 21.7%, P<0.001), heartburn (33.1% vs. 16.8%, P<0.001), dysphagia (28.5% vs. 18.3%, P<0.001), aerophagia (24.7% vs. 12.3%, P<0.001), and nausea (24.7% vs. 7.2%, P<0.001) were all significantly greater in the EDS population compared with MFS population. The prevalence of FGIDs was similar across subtypes of EDS. In general, participants with EDS were more likely to have nearly all pelvic floor symptoms as compared with participants with MFS. CONCLUSIONS: The prevalence of FGIDs and pelvic floor symptoms in EDS is higher than that found in MFS. The prevalence of FGIDs were similar across EDS subtypes. This study supports the mounting evidence for FGIDs in those with connective tissue diseases, but more specifically, in EDS.

Emergency Department Burden of Gastroparesis in the United States, 2006 to 2013.

BACKGROUND AND AIMS: Gastroparesis, a chronic gastrointestinal disorder defined by delayed stomach emptying in the absence of obstruction, is often associated with frequent and costly visits to the emergency department (ED). The aim of this study was to analyze trends in gastroparesis-related ED visits from 2006 to 2013. MATERIALS AND METHODS: Patients with a primary diagnosis of gastroparesis were identified from the Nationwide Emergency Department Sample (NEDS), the largest publicly available ED all-payer representative database in the United States. ED visits, admission rates, duration of hospitalizations, and charges were compiled. Patients with a secondary diagnosis of diabetes mellitus were analyzed as a subgroup. RESULTS: The number of ED visits for gastroparesis as a primary diagnosis in the United States increased from 15,459 in 2006 to 36,820 in 2013, an increase from 12.9 to 27.3 per 100,000 ED visits. The total charges associated with these ED visits and subsequent admissions increased from $286 million to $592 million. In contrast, admission rates through the ED decreased by 22%, procedure rates decreased by 6.2%, and the mean length of stay was shortened by 0.6 days. ED visits for patients with diabetic gastroparesis increased from 5696 to 14,114, an increase from 4.7 to 10.5 per 100,000 ED visits, with an increase in total associated charges for ED visits and subsequent admissions from $84 million to $182 million. CONCLUSIONS: The number of ED visits and associated charges for a primary diagnosis of gastroparesis with or without a secondary diagnosis of diabetes mellitus rose significantly from 2006 to 2013.

Significant Morbidity and Mortality Associated with Fecal Impaction in Patients Who Present to the Emergency Department.

BACKGROUND: Fecal impaction (FI) is defined as a large mass of stool in the rectum and/or colon that is unable to be evacuated. No study to date details demographics and outcomes in a sizeable sample of FI patients in the USA. AIMS: The present study aims to develop knowledge of FI by reporting descriptive measures and outcomes of patients presenting to a US emergency department (ED) with FI. METHODS: Medical charts coded with FI at Beth Israel Deaconess Medical Center from 2016 or 2017 were identified retrospectively. Patients diagnosed with FI in the ED or subsequent to direct hospital admission from the ED were included. Patient-specific demographics, visit-specific details, medical and medication histories, and hospital treatment and outcome measures were included in a database and analyzed. RESULTS: Thirty-two patients (mean age of 72.9 years, 62.5% female) had a total of 42 ED visits with FI. Patients had an average of 8.7 diagnoses and 11.2 medications listed in their charts. 54.8% of patients were taking at least one commonly prescribed constipating medication. The median total length of stay for admitted patients was 3 days, with nearly 90% of the ED visits with FI requiring hospital admission. 40.6% of patients experienced serious FI-related morbidities, and 21.9% of patients with FI died in the hospital. CONCLUSION: Patients presenting with FI had high risk of morbidity and mortality, complex medical histories, and large numbers of active treatment regimens. Patients with FI should receive immediate treatment and close monitoring for morbidities and complications.

Prevalence of Chronic Constipation and Chronic Diarrhea in Diabetic Individuals in the United States.

INTRODUCTION: Diabetic individuals commonly report disordered bowel habits. This study aims to report the prevalence and associated factors of chronic diarrhea (CD) and chronic constipation (CC) in diabetics using a nationally representative sample of US adults. METHODS: Analyses were performed using data from subjects in the 2009-2010 National Health and Nutrition Examination Survey (NHANES) dataset who completed the Bowel Health Questionnaire. The NHANES dataset provides medical comorbidities, demographics, and dietary habits of a nationally representative group of adult survey participants in the United States. CC and CD were defined by Bristol Stool Form Scale (BSFS) Types 1 & 2 and BSFS Types 6 & 7 as the "usual or most common stool type," respectively, and frequent laxative users were also defined as having CC. Co-variables for all subjects included demographic and lifestyle factors, and co-variables evaluated only in diabetics included treatment and severity markers for diabetes. RESULTS: We identified 661 diabetic subjects and 4488 non-diabetic subjects. Diabetic subjects (25.8%) reported disordered bowel habits. In unadjusted analysis, CD was more prevalent in diabetics than in non-diabetics (11.2% vs. 6.0%; p < 0.0001); however, the prevalence of CC was not significantly different between groups (14.6% vs. 11.2%; p = 0.126). When adjusting for covariates (e.g., BMI, gender, age, race/ethnicity, education level, etc.), diabetes itself remained associated with CD. Diabetic individuals with CD more frequently used drugs to lower blood sugar, and diabetic subjects with CC more frequently had poor kidney function. CONCLUSIONS: CD is significantly more prevalent in diabetics than in non-diabetics, whereas CC is not, and the association between CD and diabetes remains significant when adjusting for covariates. Use of medications that lower blood sugar is associated with CD in diabetic individuals, whereas poor kidney function is associated with CC in diabetics.

Clinical and manometric characteristics of women with paradoxical puborectalis syndrome.

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.

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

BACKGROUND: Poor sleep quality is common among patients with gastrointestinal (GI) disorders. However, few studies have assessed the presence of insomnia or reported circadian preferences and none have directly compared sleep between common GI conditions. AIMS: To compare clinical sleep characteristics in patients presenting to a tertiary care GI clinic for irritable bowel syndrome (IBS), functional dyspepsia (FD), inflammatory bowel disease (IBD), gastroesophageal reflux disease (GERD), and celiac disease (CD). METHODS: Validated sleep measures were administered to consecutive patients if they were diagnosed with IBS, IBD in clinical remission, CD, FD, or GERD. Healthy Controls (HCs) with no reported GI diagnoses or symptoms were also recruited. RESULTS: A total of 212 eligible respondents completed this survey, 161 GI clinic patients (IBS (n = 48), GERD (n = 29), IBD in clinical remission (n = 44), CD (n = 40)), and 41 HCs. Only, 10 respondents had a diagnosis of FD, and these were excluded. The IBS group had the highest frequency of poor sleep (72%) followed by CD (61%), GERD (60%), IBD (54%), and HC (39%). IBS patients also had the highest frequency of clinical insomnia (51%), followed by GERD (37%), CD (35%), IBD (27%), and HC (18%). 40% of IBS patients reported taking sleep medications at least once per week, compared to 32% of GERD, 23% IBD, 13% CD, and 15% HC. CONCLUSIONS: Patients presenting to a tertiary care GI clinic report poorer sleep than healthy controls. In general, patients with IBS report the highest rates of sleep difficulties compared to patients with other diagnoses.

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

BACKGROUND & AIMS: A high proportion of patients with irritable bowel syndrome (IBS) respond to placebo in clinical trials (estimated at about 40%). We aimed to identify factors that contribute to the high placebo response rate using data from a placebo-controlled trial of patients with IBS. METHODS: We performed a retrospective analysis of 599 women with IBS with constipation who were in the placebo group of a 12-week, randomized, double-blind, phase 3 trial of the experimental medication renzapride. Primary analyses evaluated frequency of abdominal pain in patients who received placebo, defined as ≥30% pain improvement from baseline for ≥6 of the 12 study weeks. We performed backward elimination regression with bootstrapping to identify factors associated with response to placebo. RESULTS: In the placebo group, 29.0% of the patients had an abdominal pain response. Factors associated with a response to placebo were baseline variation in abdominal pain (odds ratio [OR], 1.71), maximum baseline pain severity (OR, 1.34), and placebo response in study week 2 (OR, 2.23) or week 3 (OR, 3.69). Factors associated with lack of response to placebo were number of baseline complete spontaneous bowel movements (OR, 0.73; P = .019) and final baseline pain ratings (OR, 0.73; P < .001). CONCLUSIONS: We identified factors associated with a response in abdominal pain to placebo using original data from an IBS clinical trial. Baseline factors associated with the placebo response in women with IBS and constipation included variation in baseline pain symptoms, severity of baseline symptoms, and early improvement of abdominal pain. These findings have significant implications for clinical trial design.

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

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.

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

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 µ-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 µ-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, µ-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 µ-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 µ-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.

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 Nausea and Vomiting Associated With Cannabis Use Disorder: US Trends From 2006 to 2013.

BACKGROUND AND AIMS: Chronic cannabis use is associated with nausea and vomiting that may lead to emergency department (ED) visits, multiple diagnostic tests, and procedures. The aim of this study was to analyze recent trends in ED visits for vomiting associated with cannabis use disorder between 2006 and 2013. METHODS: Data were obtained from the National Emergency Department Sample records in which vomiting (ICD-9-CM codes 787.01, 787.03, and 536.2) was a primary diagnosis in combination with cannabis abuse or dependence (304.3, 304.30, 304.31, 304.32, 304.33, 305.2, 305.20, 305.21, 305.22, and 305.23) and were seen in the ED between 2006 and 2013. The National Emergency Department Sample collects data from more than 25 million visits in over 950 EDs and is weighted to provide national estimates. RESULTS: The rate of ED visits for vomiting with cannabis use disorder from 2006 compared with 2013 increased from 2.3 to 13.3 per 100,000 ED visits, while the mean inflation-adjusted costs increased 68.5% from $2758.43 to $4647.62, respectively. Men between the ages of 20 and 29 were the most common group to present to the ED for vomiting with cannabis use disorder. The Midwest and West had the higher rates of ED visits for vomiting with cannabis use disorder compared with the Northeast and South. CONCLUSIONS: ED visits for vomiting associated with cannabis use disorder is common and is associated with significant medical costs. Further research on the role of cannabis use in nausea and vomiting is warranted.

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

BACKGROUND: Placebo 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 DESIGN: This 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. DISCUSSION: OLP 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 REGISTRATION: ClinicalTrials.gov, identifier: NCT02802241 . Registered on 14 June 2016.

Emergency Department Burden of Diverticulitis in the USA, 2006-2013.

GOALS: The aim of this study was to analyze recent trends in emergency department (ED) visits for diverticulitis between 2006 and 2013. BACKGROUND: Acute diverticulitis is a serious medical condition that frequently leads to ED visits, hospitalizations, and surgeries resulting in a significant health care burden. METHODS: Data 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. RESULTS: Between 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 $822 million in 2006 to over $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. CONCLUSIONS: The 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.