Citations

INTRODUCTION: Gastric-emptying scintigraphy (GES), routinely used to measure gastric emptying, is an essential tool to diagnose gastroparesis. An accurate diagnosis of gastroparesis relies upon the GES being performed according to a validated protocol. Jointly published protocol guidelines have been available for over a decade; however, the extent to which these guidelines are adhered to is unknown. This study aimed to assess national compliance with established GES protocol guidelines. METHODS: We developed a questionnaire addressing key protocol measures outlined in the published Procedure Guideline for Adult Solid-Meal Gastric Emptying Study 3.0. Survey questions addressed patient information collection (15), patient preparation and procedure protocol (16), meal content and preparation (7), imaging (3), interpretation (4), and reporting (7). Demographic data was also collected. The anonymous questionnaire was distributed electronically to members of the Society of Nuclear Medicine and Medical Imaging (SNMMI) and non-member recipients of the SNMMI daily email newsletter. One response per medical institution was permitted. Data were entered manually and statistically assessed using JMP®, Version 14.0. SAS Institute Inc., Cary, NC. RESULTS: 121 medical institutions (MI) responded; 49 (40.4%) were academic/teaching medical centers. The mean number of annual GES procedures was 199.9 (range, 5 to 2000 GES/year). On average, MI performed 64% (33.5/52) of protocol measures according to guidelines while academic medical centers performed 61% (31.5/52) of protocol measures according to guidelines. Only 59% of MI use the validated meal. 42% of MI reported stopping imaging prior to the validated 4-hour interval. Only 16% of MI test blood glucose levels prior to GES while 71% cancel or reschedule GES if blood glucose levels are above the validated cut-off. 68% of MI ask patients if they take narcotic pain medications; only 49% require that patients stop taking narcotic pain medications at least two days prior to the GES. Only 4.5% of MI perform GES while adhering to 3 critical measures: validated study duration; controlling blood glucose levels; and properly restricting medication use. CONCLUSION: Low compliance with GES protocol guidelines, even among academic medical centers, raises the likely possibility of misdiagnosis and thus improper management of upper gastrointestinal symptoms. These results highlight a need for increased awareness of protocol guidelines.

INTRODUCTION: Bowel preps for colonoscopy can cause transient changes in gut microbiota. Rifaximin is indicated as IBS-D treatment in adults. This post hoc analysis evaluated effect of time since colonoscopy on rifaximin response for IBS-D. METHODS: Two phase 3 studies (TARGET 1/2) comprised adults who had documented history of colonoscopy <2 y prior to enrollment for IBS evaluation; otherwise they had 1 within 30 d of signed consent. Patients (pts) were randomized to rifaximin 550 mg TID or placebo for 2 wks. Responders, grouped by time from colonoscopy to treatment start (≤60 d or >60 d), were analyzed using LOCF. Composite responders (FDA endpoint) were pts meeting weekly response criteria for abdominal pain (≥30% decrease from baseline in mean weekly pain score [range, 0-6]) and stool consistency (≥50% decrease from baseline in d/wk with Bristol Stool Scale type 6/7 stool) during ≥2 of first 4 wks posttreatment; responders for individual components also were determined. RESULTS: Differences in responder rates between rifaximin and placebo were observed in colonoscopy-timing subgroups (≤60 d or >60 d), with largest differences seen in >60 d group (Figure 1). Among pts who had colonoscopy >60 d prior to starting treatment in TARGET 1, a greater percentage treated with rifaximin (n=109) vs placebo (n=106) were composite (47.7% vs 34.0%; P = 0.04), abdominal pain (53.2% vs 40.6%; P = 0.06), or stool consistency (81.7% vs 63.2%; P = 0.002) responders. For colonoscopy ≤60 d prior to starting treatment, a greater percentage of pts treated with rifaximin (n = 199) vs placebo (n = 208) were composite (45.7% vs 40.9%; P = 0.32), abdominal pain (50.3% vs 42.8%; P = 0.13), or stool consistency (77.4% vs 69.7%; P = 0.08) responders. In TARGET 2, a greater percentage of pts treated with rifaximin (n = 106) vs placebo (n = 97) in colonoscopy >60 d prior group were composite (45.3% vs 32.0%; P = 0.05), abdominal pain (53.8% vs 39.2%; P = 0.04), or stool consistency (71.7% vs 61.9%; P = 0.14) responders. A greater percentage of pts treated with rifaximin (n = 209) vs placebo (n = 223) in colonoscopy ≤60 d prior group were responders, although differences were smaller: composite (47.4% vs 38.1%; P = 0.05), abdominal pain (51.7% vs 44.8%; P = 0.16), and stool consistency (75.1% vs 65.5%; P = 0.03). CONCLUSION: Larger differences in responder rates with rifaximin vs placebo were observed in pts in whom colonoscopy was >60 d from start of IBS-D therapy. This may be related in part to reestablishment of IBS-related gut microbiota dysbiosis; further research is needed.

INTRODUCTION: Functional Dyspepsia (FD) is a common functional GI disorder in the upper abdomen (above the navel). The estimated prevalence is 15-30% worldwide. There are currently no FDA-approved medications for the treatment of FD. Proton pump inhibitors (PPIs) are commonly prescribed off-label. However, long-term use of these drugs has been associated with serious health concerns. Prokinetic agents are also often used off-label. However, many are associated with significant side effects (e.g. metoclopramide). A safe, effective, and readily available treatment option for FD is greatly needed. This study describes an important 24-month post-marketing point on an option for FD that has already demonstrated good efficacy and low side effects in RCTs. These RCTs have demonstrated that the combination of caraway oil and peppermint oil improves FD symptoms. Caraway oil plus L-menthol (the major component of peppermint oil) with site-specific targeting (COLM-SST) is a novel delivery system of triple-coated, solid-state microspheres designed to target the duodenum, the main center of disturbance in FD. This study was conducted to report on the overall safety profile of COLM-SST and to determine if any unexpected pattern of side effects emerged. METHODS: A call-in number for reporting adverse events (AEs) was provided on all boxes containing COLM-SST. An independent call center with pharmacovigilance-trained health care personnel, in accordance with the FDA and global regulatory guidelines on properly reporting AEs, was retained to receive and record customer AEs. The AEs for this study were collected and processed from July 8, 2016 to July 8, 2018. RESULTS: An estimated 558,345 individual patients used COLM-SST during the surveillance. An analysis of the data showed that there were no serious AEs reported. Additionally, the self-reporting rate of non-serious AEs was low, with only 148 events received (from 127 patients), a 0.023% event rate for COLM-SST. The top reported, non-serious AEs were abdominal pain/discomfort/distension (18; 0.0032%), which were consistent with the pattern of commonly reported symptoms of FD, and headache (7; 0.0013%). CONCLUSION: 24 months of monitoring in-market, real-world use of caraway oil and L-menthol with site-specific targeting, for the treatment of FD demonstrates an extremely low rate of self-reported AEs. These data, combined with earlier RCT data, indicates that COLM-SST is a safe and effective therapy for FD, and is a viable alternative to PPIs and prokinetics.

INTRODUCTION: High-resolution manometry using the Chicago Classification is standard in the evaluation of esophageal motility. When the relaxation of the esophagogastric junction is impaired and achalasia excluded, esophagogastric junction outflow obstruction (EGJ-OO) is diagnosed and the esophageal body is essentially ignored. We sought to characterize the function of the esophageal body in consecutive patients with EGJ-OO. METHODS: Retrospective review of the esophageal manometry findings in consecutive patients where there was computer recognition of EGJ-OO collected over a 2-month period. In each case, the esophageal body was reviewed manually and results reported independent of the suggested computer diagnosis. RESULTS: 116 patients underwent manometry over a 2-month period and 30 (26%) were identified as having EGJ-OO. The indications for testing included chronic cough (n = 5), GERD (n = 8), dysphagia (n = 9) and esophageal evaluation associated with severe lung disease or transplantation (n = 8). The mean IRP was 20.8 (range 16-33.6) and did not vary depending on indication ( P = 0.381). Computer interpretation was EGJ-OO in all patients without mention of the esophageal body. After review, 11 (37%) had an additional esophageal diagnosis. In effective esophageal motility (IEM) was the most prevalent among them (IEM-8, achalasia-2, jackhammer esophagus-1; P = 0.020). The frequency of an additional esophageal diagnosis was significantly different between GERD (0%) and dysphagia (66%; P = 0.004), but not between other groups (i.e. 40% in cough and 37.5% in transplant group). An esophageal body diagnosis was significantly more likely in patients with IRP > 25 (80%) compared with those with IRP < 25 (28%; P = 0.028). CONCLUSION: 1-EGJ-OO is common in patients referred for esophageal manometry. 2-An additional esophageal body diagnosis is common in those with EGJ-OO.3-Esophageal diagnoses are more common in patients with dysphagia and in those with a very high IRP. The body of the esophagus is important in cases of EGJ-OO and should be reported independent of the computer-generated interpretation of the Chicago Classification.

INTRODUCTION: Most Americans consume only half of the daily fiber recommended by the National Academy of Medicine, which is 25 grams per day of fiber for women and 38 grams per day for men. Fiber has been shown to promote bowel regularity, lower cholesterol, control blood sugar, and maintain body weight. To fill the “fiber gap” many patients use fiber supplements. There is a perception that fiber supplementation can lead to bloating and excess gas production, among other adverse events. This study aimed to examine whether or not a pattern of adverse events was associated with chewable inulin fiber (CIF). METHODS: A call-in number for reporting adverse events (AEs) was provided on bottles of a specific brand of CIF. An independent call center with pharmacovigilance-trained health care personnel in accordance with the FDA and global regulatory guidelines on properly reporting AEs was retained to receive and record customer AEs. The AEs for this study were collected and processed from January 1, 2018 to December 31, 2018. RESULTS: An estimated 809,259 individual patients consumed CIF during the surveillance. An analysis of the data showed that there were no serious AEs reported. Additionally, the self-reporting rate of non-serious AEs was low, with only 23 non-serious events reported by 21 individuals; a rate of 2.8 per 100,000 users. The top reported, non-serious AEs were flatulence, diarrhea, and constipation; however, the rates for these were extremely low (4.9, 3.7, and 1.2 per million, respectively). Two events were reported that were classified as musculoskeletal and connective tissue disorders; however, these were considered to not be related, having no basis for biological plausibility. CONCLUSION: 12 months of monitoring real-world use of CIF in a population of over 800,000 patients demonstrates an extremely low rate of self-reported AEs. Contrary to conventional thinking, the rate of flatulence was remarkably low (4.9 per million users), and can most likely be considered statistical background noise. These data, combined with previous RCTs, indicates that CIF is a safe and effective option for fiber supplementation.

Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) condition involving numerous potential causative factors (e.g. alterations in gut microbiota, motility, brain–gut axis). Several interventions are available for the management of patients with IBS, but no universal management algorithm currently exists. The aim of this article is to review interventions that may be considered in the management of patients with IBS with diarrhea (IBS-D). Nonpharmacological interventions include dietary and lifestyle modification, which are generally used as first-line therapy. Probiotics have demonstrated efficacy and safety in patients with IBS, but studies are inconsistent in strains examined, dosing, and treatment duration. Psychological therapies (e.g. cognitive behavioral therapy, hypnotherapy) also may improve IBS symptoms. Pharmacological interventions for the management of IBS-D include the US Food and Drug Administration–approved agents eluxadoline, rifaximin, and alosetron, as well as loperamide, smooth muscle antispasmodics, bile acid sequestrants, and antidepressants (i.e. tricyclic antidepressants, selective serotonin reuptake inhibitors). Eluxadoline and rifaximin have been shown to improve abdominal pain and stool consistency in patients with IBS-D. In addition, data indicate that alosetron improves IBS symptoms; however, it is approved only for women with severe IBS-D. Of the three approved agents, rifaximin has the most favorable safety profile. The risk–benefit ratio is an important consideration with every medication, but is especially important in the treatment of functional GI disorders such as IBS-D. Thus, the most troublesome symptoms, quality of life, symptom intensity, and individual patient preferences should be considered when formulating a management plan for patients with IBS-D.

SummaryIbrutinib‐related data in Waldenström macroglobulinaemia (WM) remain sparse, particularly outside of trials. We report on 80 patients [previously treated, n = 67 (84%), treatment‐naïve, n = 13 (16%)] with WM, evaluated consecutively at Mayo Clinic, who received ibrutinib off‐study after its approval in 2015 for WM. Overall response rate (ORR) was 91%; major‐response rate (MRR) was 78%. The median time to first response and best response was 2·9 [95% confidence interval (CI): 2–4] and 5·7 (95% CI: 4–12) months, respectively. The median follow‐up was 19 (95% CI: 14–21) months; 18‐month progression‐free survival (PFS) was 82%. The median time on therapy was 12·5 (95% CI: 9·3–16·7) months, and the median duration‐of‐response was 32 (range: 23–32) months. Twenty‐five patients (31%) had discontinued therapy at last follow‐up (68% due to treatment‐related toxicities) and 18% of patients required dose reduction. Fatigue (12%) and atrial‐fibrillation (11%) were common non‐haematological toxicities. IgM rebound occurred in 36% of patients who abruptly discontinued ibrutinib. Following ibrutinib discontinuation, 84% of patients received subsequent treatment, achieving an ORR of 57% and MRR of 50%. The median PFS from commencement of subsequent salvage therapy was 18 months. Ibrutinib therapy, outside of clinical trials, is effective in WM, but is associated with toxicities and challenges, including IgM rebound and a high drug discontinuation rate for reasons other than disease progression.

OBJECTIVE: Data regarding opioid effects on esophageal function are limited. We previously demonstrated an association between chronic opioid use and esophageal motor dysfunction characterized by esophagogastric junction outflow obstruction, distal esophageal spasm, achalasia type III, and possibly Jackhammer esophagus. Our aim was to characterize the influence of different opioids and doses on esophageal dysfunction. METHODS: Retrospective review of 225 patients prescribed oxycodone, hydrocodone, or tramadol for >3 months, who completed high-resolution manometry from 2012 to 2017. Demographic and manometric data were extracted from a prospectively maintained motility database. Frequency of opioid-induced esophageal dysfunction (OIED, defined as distal esophageal spasm, esophagogastric junction outflow obstruction, achalasia type III, or Jackhammer esophagus on high-resolution manometry, was compared among different opioids. The total 24-hour opioid doses for oxycodone, hydrocodone, and tramadol were converted to a morphine equivalent for dose effect analysis. RESULTS: OIED was present in 24% (55 of 225) of opioid users. OIED was significantly more prevalent with oxycodone or hydrocodone use compared with tramadol (31% vs 28% vs 12%, P = 0.0162), and for oxycodone alone vs oxycodone with acetaminophen (43% vs 21%, P = 0.0482). There was no difference in OIED for patients taking hydrocodone alone vs hydrocodone with acetaminophen. Patients with OIED were taking a higher median 24-hour opioid dose than those without OIED (45 vs 30 mg, P = 0.058). DISCUSSION: OIED is more prevalent in patients taking oxycodone or hydrocodone compared with tramadol. There is greater likelihood of OIED developing with higher doses. Reducing the opioid dose or changing to tramadol may reduce OIED in opioid users.