A novel duodenal-release formulation of caraway oil and L-menthol is a safe, effective and well tolerated therapy for functional dyspepsia.

BACKGROUND: A randomized, placebo-controlled clinical trial (FDREST) of a novel formulation of caraway oil and L-menthol (COLM-SST) demonstrated symptom relief in patients with functional dyspepsia (FD). Two follow-up studies were conducted to evaluate patient satisfaction, self-regulated dosing, and long-term safety data: FDACT, Functional Dyspepsia Adherence and Compliance Trial, and FDSU36, Functional Dyspepsia Safety Update at 36 months. METHODS: A patient reported outcomes (PRO) questionnaire was designed and distributed online to assess real-world satisfaction and dosing frequency of open-label COLM-SST in patients with FD. A separate study analyzing voluntary safety surveillance data evaluated the frequency and severity of reported adverse events (AEs). RESULTS: A total of 600 FD patients were enrolled in the PRO study. Ninety five percent of respondents reported a major or moderate improvement in their FD symptoms and 91.7% indicated a major or moderate improvement in quality of life (QOL) using COLM-SST. Between 1 and 4 capsules were consumed daily by 91.2% of respondents, with 56.2% taking them before meals. Symptom relief was rapid, with 86.4% of respondents indicating relief within 2 h of taking COLM-SST. Few adverse events (AEs) were reported (0.0187%) by patients using COLM-SST. No serious AEs were identified. CONCLUSION: COLM-SST is safe, well tolerated, and provides rapid relief of FD symptoms. These findings, demonstrated in the FDREST trial, were further supported by a large prospective PRO study evaluating self-regulated dosing frequency, symptom improvement, and QOL. COLM-SST was well-tolerated based on review of AE data at 36 months.

Patient experience with NER1006 as a bowel preparation for colonoscopy: a prospective, multicenter US survey.

BACKGROUND: NER1006 (Plenvu®, Salix Pharmaceuticals, Bridgewater, NJ) is a 1 L polyethylene glycol bowel preparation indicated for colonoscopy in adults. A US online survey assessed real-world ease of use and treatment satisfaction in individuals who received NER1006. METHODS: Adults were recruited from 444 US community gastrointestinal practices and provided a kit number for enrollment into an online survey to be completed within 2 weeks. Survey questions evaluated colonoscopy history and prior bowel preparation(s) prescribed, patient experience during NER1006 administration, and patient satisfaction with the bowel preparation process. A 9-point predefined grading scale was used to evaluate ease of NER1006 preparation and consumption (range, 1 "very difficult" to 9 "very easy"); the perceived importance of volume requirement and clear liquid options (range, 1 "not important at all" to 9 "very important"); and patient satisfaction (range, 1 "not satisfied at all" to 9 "very satisfied"). RESULTS: 1630 patients were enrolled, 1606 underwent colonoscopy, and 1598 completed the survey between September 15, 2018 and February 28, 2019. Among 1606 patients who had a colonoscopy, 62.5% were female, and the mean patient age was 54.4 years (range 18-89 years). Most patients (74.7%) did not report a family history of colon cancer, 62.6% had undergone prior colonoscopy, and 64.8% were undergoing colonoscopy for routine colorectal cancer screening. A majority (76.1%) of patients who completed the survey reported that NER1006 was very easy to prepare and take, and 89.9% were very or moderately satisfied with NER1006 overall. Most (97.6%) patients reported consuming all or most of the bowel preparation. Among 1005 patients with previous bowel preparation use, 84.7% indicated that their experience with NER1006 was much better or better (65.3%) or about the same (19.4%) compared with previously used bowel preparations, while only 15.3% rated NER1006 as worse or much worse. CONCLUSIONS: In this first real-world, US multicenter survey, patient-reported experience with NER1006 as a bowel preparation for colonoscopy was favorable and adherence was high. The majority of patients were very or moderately satisfied with the overall experience and found it much better/better than previously used bowel preparations. TRIAL REGISTRATION: Not applicable.

Novel 1 L polyethylene glycol-based bowel preparation NER1006 for overall and right-sided colon cleansing: a randomized controlled phase 3 trial versus trisulfate.

BACKGROUND AND AIMS: NER1006 is the first 32 fluid ounce (1 L) polyethylene glycol-based bowel preparation. This randomized, multicenter, colonoscopist/central reader-blinded phase 3 non-inferiority trial assessed the efficacy, safety, and tolerability of NER1006 versus trisulfate for bowel cleansing. METHODS: Patients undergoing colonoscopy were randomized (1:1) to receive NER1006 or trisulfate, using evening/morning split-dosing administration. Blinded central readers used the validated Harefield Cleansing Scale to evaluate 2 alternative primary endpoints: overall bowel-cleansing success and high-quality cleansing of the ascending colon/cecum. Secondary endpoints included lesion detection, Boston Bowel Preparation Scale (BBPS) assessment, and adherence. The non-inferiority margin was 10% and the significance threshold was P < .025. RESULTS: Of 621 patients randomized (NER1006, n=310; trisulfate, n=311), 556 were evaluated for efficacy (NER1006, n=276; trisulfate, n=280). NER1006 achieved non-inferiority versus trisulfate for both primary endpoints of overall bowel-cleansing success (85.1% vs 85.0%; difference, 0.14%; one-sided 97.5% lower confidence limit [LCL], -8.15%; P = .528) and high-quality cleansing of the ascending colon/cecum (35.9% versus 29.3%; difference, 6.58%; LCL, -1.69%; P = .059). BBPS assessments supported overall bowel-cleansing success rates. Lesion detection rates were similar between the groups. The percentage of patients with treatment-related adverse events was 14.9% with NER1006 and 9.4% with trisulfate. Both bowel preparations showed similar overall tolerability and safety profiles. Adherence was very high in both arms. CONCLUSIONS: With evening/morning split dosing, NER1006 was as effective as trisulfate for overall bowel and right-sided colon cleansing. Adverse event rates were slightly higher with NER1006 than trisulfate, but did not compromise tolerability, adherence, or efficacy. (Clinical trial registration number: NCT02254486.).

A Novel Delivery System of Peppermint Oil Is an Effective Therapy for Irritable Bowel Syndrome Symptoms.

BACKGROUND: Peppermint oil (PO) has shown promise as an IBS therapy, but previous trials have demonstrated variable efficacy and tolerability results. AIMS: To evaluate the efficacy and tolerability of a novel formulation of PO designed for sustained release in the small intestine in patients with IBS-M and IBS-D. METHODS: This is a 4-week, randomized, double-blind, placebo-controlled clinical trial of PO or identical placebo 3 times daily in patients fulfilling Rome III criteria for IBS-M or IBS-D. The primary endpoint was the change from baseline in the Total IBS Symptom Score (TISS) after 4 weeks of treatment. RESULTS: Seventy-two patients (mean age 40.7 years, 75 % female, 77.8 % white) were randomized to PO (n = 35) or placebo (n = 37). At 4 weeks, PO was associated with a 40 % reduction in the TISS from baseline (mean change -1.16, SD ± 0.807), superior to the 24.3 % decrease (mean change -0.70, SD ± 0.737) observed with placebo (P = 0.0246). The decrease in the TISS of 19.6 % (mean change -0.55, SD ± 0.613) in the PO group at 24 h was also significantly larger than placebo (-10.3 %, mean change -0.27, SD ± 0.342) (P = 0.0092). At trial completion, patients in the PO group experienced greater improvement in multiple individual gastrointestinal symptoms as well as in severe or unbearable symptoms, compared to placebo. PO was well tolerated with few adverse events. CONCLUSIONS: A novel PO formulation designed for sustained release in the small intestine is a safe, effective treatment capable of providing rapid relief of IBS symptoms.

Biosimilars: the need, the challenge, the future: the FDA perspective.

OBJECTIVES: This article summarizes the brief history of the biosimilars industry, the FDA's regulations and guidance for biosimilars development, and the issues and challenges facing developers and regulators in bringing biosimilars to market. METHODS: Current literature, regulations, and FDA guidance documents were summarized and interpreted to define biosimilars and to present their financial and clinical implications. RESULTS: Some biologic agents that will lose patent protection during the next few years may be replaced with lower cost follow-on biologics. However, unlike generic drugs, biosimilars may be structurally and functionally different from the reference product they are designed to resemble. The FDA has yet to approve any agent via the abbreviated licensure pathway for biosimilars that was passed as part of the Affordable Care Act. The FDA has issued new guidance describing processes by which manufacturers may demonstrate either biosimilarity or interchangeability with an FDA-approved biologic agent, which is required for abbreviated licensure. Biosimilars approved in Europe consist of relatively small molecules; complex large-molecule biosimilars could be subjected to a rigorous and prolonged FDA approval process, which would defeat attempts to develop lower-cost versions of biologic drugs. CONCLUSIONS: Biosimilar development is a consequence of the financial success of biologic therapies and their eventual patent expiration. The pharmaceutical industry must now develop complex biosimilars that resemble FDA-approved biologic agents and invent analytical tools and end points to demonstrate similarity to regulatory authorities. Already in development is a new wave of "biobetter" or "biosuperior" drugs that mimic but also improve upon a biologic drug's chemistry, formulation, or delivery.

Novel endoscopic delivery modality of infrared coagulation therapy for internal hemorrhoids.

BACKGROUND: A novel endoscopic delivery system for infrared coagulation therapy (IRC) has been designed recently. IRC is a well-established treatment for symptomatic internal hemorrhoids. Patients frequently undergo lower endoscopy before hemorrhoid treatment to eliminate other sources of bleeding. Current treatment options are difficult to perform without an anal retractor, adequate lighting, and specialized instruments. Endoscopic IRC is an attractive alternative to standard IRC, because it can be performed during the lower endoscopy. TECHNIQUE: Endoscopic IRC utilizes infrared radiation generated by a control box, which is applied to the tissue through a flexible, fiber optic light guide (Precision Endoscopic Infrared Coagulator™). The light guide is placed through the colonoscope or flexible sigmoidoscope in the same chamber as other endoscopic instruments. METHODS: A retrospective review was performed using a prospectively collected database. A standardized protocol was utilized in all patients. Patients graded their symptoms before and after therapy by using the visual analog symptom severity scoring system (range, 0-10). These results were analyzed by using the nonparametric Wilcoxon signed-rank test. Exact P values were computed by using the R function wilcox.exact. RESULTS: A total of 55 patients underwent endoscopic IRC for predominately grade II and grade III symptomatic internal hemorrhoids (71 %). There were 22 (40 %) female patients. Posttherapy results indicated a significant improvement in global symptoms (pretreatment average global score = 2.24 vs. posttreatment average global score = 0.28; P < 0.0001). There have been no adverse events reported to date. CONCLUSIONS: Endoscopic IRC provides improved visibility and efficiency, allowing simultaneous treatment of symptomatic internal hemorrhoids at the time of lower endoscopy. Patients experienced significant improvement in their symptoms after a single session of endoscopic IRC. There are a variety of additional endoscopic IRC therapeutic utilities: endoscopic management of angiodysplasia, inflammation, hemostasis, and NOTES applications.

High-quality colon cleansing and multiple neoplasia detection with 1L NER1006 versus mid-volume options: Post hoc analysis of phase 3 clinical trials.

Background and study aims Multiple neoplasia increase the risk of colorectal cancer. High-quality cleansing may improve adenoma detection. We assessed whether a new bowel preparation can improve colon cleansing and multiple lesion detection. Patients and methods This post hoc analysis of two randomized clinical trials in Europe and the US assessed the per study and combined cleansing efficacy of overnight split dosing with (preparation + clear fluids) 1 + 1 L polyethylene glycol (PEG) NER1006 versus 2 + 1 L PEG + ascorbate (2LPEG) or 1 + 2 L oral sulfate solution (OSS) combined. Treatment-blinded central readers assessed cleansing quality using the Harefield Cleansing Scale (HCS). Patients with full segmental scoring were included. HCS segmental scores 0-4 (high-quality = HCS 3-4) were analyzed for NER1006 versus 2LPEG/OSS. Mean number of polyps or adenomas per patient (MPP/MAP) was calculated for treatments in patients with at least one polyp or adenoma. Results In 1037 patients, NER1006 attained a greater rate of HCS 3 scores (29 % vs. 20 %; P  < 0.001) and HCS 4 scores (20 % vs. 17 %; P  = 0.007) versus 2LPEG/OSS. More polyps (678 versus 585) and adenomas (397 versus 331) were detected with NER1006 (N = 517) versus 2LPEG/OSS (N = 520). In all neoplasia-positive patients, with increasing minimal per-patient neoplasia multiplicity from 1 to 10, NER1006 numerically improved MPP (difference ± SE: 0.48 ±â€Š0.24 to 3.89 ±â€Š3.37) and MAP (0.47 ±â€Š0.26 to 7.50 ±â€Š9.00) versus 2LPEG/OSS. Conclusions Low-volume NER1006 enhances high-quality cleansing versus medium-volume 2LPEG or OSS, individually and when combined. NER1006 may consequently facilitate the detection of multiple neoplasia in patients.

Nondestructive Determination of the Age of 20th-Century Oil-Binder Ink Prints Using Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR FT-IR): A Case Study with Postage Stamps from the Lódz Ghetto.

The ability to determine the production date for a painting or print would be of great benefit in the forensic detection of fakes and forgeries as well as in art history and conservation. Changes in the pigments used at different times have been invaluable in detecting incongruities that suggest fraud, but relatively little work has been published that uses the chemical changes in oil binders as they dry to determine when an ink print or an oil painting was made. Using attenuated total reflectance-Fourier transform infrared (ATR FT-IR) spectroscopy and samples with known dates, we calibrate the drying of oil binders in inks and paints and cross-validate the paints with pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS). We apply the ink calibration to a case study involving the age determination of possible philatelic counterfeits from a World War II Jewish Ghetto in Occupied Poland, obtaining a date of 1946 ± 6 (1 s, n = 9) for the genuine stamps, and 1963 ± 16 (1 s, n = 19) for the various reproductions.

Early clinical experience with networked system for promoting patient self-management.

OBJECTIVE: To gain early experience with a networked system designed to assess a patient's adherence to oral medication and physiologic metrics in an ambulatory, at-home setting. STUDY DESIGN: Prospective, observational studies. MATERIALS AND METHODS: This networked system for patient self-management consists of ingestible markers and a wearable, personal monitor. When a marker is ingested, it communicates to a monitor that time-stamps the ingestion and identifies the marker as unique. The monitor also records heart rate and activity. Data from third-party monitoring equipment (eg, sphygmomanometer, weight scale) can be integrated into the system. Collected data are summarized for patient and physician review. Directly observed ingestion (DOI) of placebo tablet markers was used to assess the system's technical performance. Markers were also coencapsulated with drugs to capture at-home adherence. A performance criterion of <95% was set as the objective for system performance. RESULTS: A total of 111 subjects ingested 7144 ingestible markers; 3298 were DOIs. The system's positive detection accuracy and negative detection accuracy in detecting ingested markers were 97.1% and 97.7%, respectively. It differentiated 100% of multiple drugs and doses taken simultaneously by type and by dose. Medication adherence was >85%. The most common adverse effect was mild skin rash from the monitor's electrodes. No definitive marker-related adverse effects were reported. CONCLUSION: The system appears to be safe and effective in capturing and integrating adherence and physiologic data. Efforts are under way to enhance system functionalities and refine user interfaces. By providing context-rich information, this system may enhance patient-provider collaboration.

The reference materials syndrome.

This paper examines specific cases in the literature where analysts using spectroscopic instrumentation report elemental concentrations that agree with information values reported in reference material certificates that are subsequently found to be incorrect.

Chemical attribution of corroded coins using X-ray fluorescence and lead isotope ratios: a case study from first century Judaea.

Nondestructive analyses using a quadrupole inductively coupled plasma-mass spectrometer (ICP-QMS) and polarizing, multi-target, energy dispersive X-ray fluorescence (PEDXRF) with three-dimensional optics were conducted on Judean coins from the first century BCE and CE to determine the efficacy and limits of these methods for numismatic analyses of coins with a patina. Comparisons with destructive analyses and literature databases demonstrate their value even when corrosion is present. An outstanding question about the dating of Herod Agrippa I or II "canopy" coins that has significance to Biblical historians is used as a case study. Multiple lines of evidence attribute this coin to Agrippa I, with a date of 41 to 45 CE, produced using Faynan (Feinan), Jordan, and Cyprus ores.