These post hoc analyses provide clinically relevant data concerning time to response for individual irritable bowel syndrome with constipation (IBS-C) symptoms after linaclotide use.
Time-to-response ...data were pooled from 4 randomized controlled trials. Response time for abdominal symptoms (pain, discomfort, and bloating) and complete spontaneous bowel movements (CSBMs) were analyzed using the Kaplan-Meier method; patients were categorized as early responders (≤4 weeks), late responders (>4-12 weeks), or nonresponders.
Among 2,350 patients (1,172 placebo and 1,178 linaclotide 290 μg), >50% of patients with IBS-C who initiated linaclotide treatment experienced a decrease of ≥30% in abdominal pain, discomfort, or bloating within 3-4 weeks (median). The median time to achieving ≥3 CSBMs was 4 weeks. Although not all linaclotide-treated patients responded within 12 weeks, a late response occurred between 4 and 12 weeks in 1 in 6 patients for abdominal pain and in approximately 1 in 10 patients for CSBM frequency. Comparisons of early responders, late responders, and nonresponders for both response definitions indicated that women, Whites, and patients with less severe baseline abdominal symptoms were more likely to respond early.
Although treatment responses with linaclotide occurred in >50% of patients with IBS-C within 4 weeks of treatment initiation, benefits for individual abdominal symptoms and/or CSBM frequency can still occur between 4 and 12 weeks. A lack of improvement in one symptom does not negate the possibility of response for others, highlighting the importance of discussing all symptoms with patients and not assuming treatment futility at 4 weeks.
Background Discriminating neoplastic from non-neoplastic polyps can significantly reduce the cost of colonoscopy. The American Society for Gastrointestinal Endoscopy (ASGE) recently set threshold ...levels for optical diagnostic accuracy to be acceptable for clinical use. Objective In this study, we compare a novel colonoscope capable of dual-focus imaging with standard colonoscopy with respect to the ASGE guidelines. Setting An academic medical center ambulatory surgical center. Patients and Interventions Patients at average risk were randomized to standard colonoscopy (Olympus CF-H180 and Exera II 180 colonoscopes, Olympus America, Center Valley, Pa) or dual-focus colonoscopy (Olympus CF-HQ190 and Exera III 190 colonoscopes, Olympus America). All polyps were given an optical diagnosis and compared with histology. Results A total of 600 patients were consented and 522 completed all aspects of the procedure. A total of 927 polyps were analyzed. Optical diagnostic accuracy was 79% (95% confidence interval, 74%-83%) for the 190 and 77% (95% confidence interval, 73%-81%) for the 180 colonoscope. Adenoma detection rates were also similar between the 2 groups (50% for the 190 vs 52% for the 180 colonoscope). For small distal rectosigmoid polyps with a high confidence diagnosis, the negative predictive value for adenoma was 96% (range 89%-99%) for the 180 in the narrow-band imaging (NBI) mode and 97% (range 88%-99%) for the 190 colonoscope in NBI mode. Agreement of surveillance intervals by using optical diagnosis was 94% to 95% for all modalities (180 and 190 colonoscopes, white light imaging, NBI). Limitations Our study evaluated the accuracy of the 180 and 190 colonoscopes at a center with already-established expertise in endoscopic imaging. Conclusions Both traditional and new dual-focus colonoscopes provide highly accurate optical polyp discrimination. There was no difference between the 2 systems in terms of discrimination or adenoma detection. Both systems are consistent with ASGE guidelines for optical diagnosis of selected colorectal polyps without histological confirmation.
The etiology of eosinophilic esophagitis (EoE) is not well understood. It has been proposed that eosinophils migrate to the esophagus in response to various ingested and inhaled allergens. Recent ...reports in children found an increased proportion of cases of EoE during months with higher outdoor aeroallergens. To our knowledge, this has not been evaluated in adults. We aimed to determine whether there is a seasonal distribution in the number of newly diagnosed cases of EoE in an adult population.
We conducted a retrospective review of consecutive adult cases newly diagnosed with EoE in 1 year. Cases were grouped based on the index month when the diagnosis was made at endoscopy. To test the consistency of the observations, a second cohort of consecutive cases of similar sample size diagnosed at a different period in time was also analyzed.
In total, 41 patients were diagnosed with EoE at our center during the study period, providing an annual prevalence of 0.98%. More cases were diagnosed with EoE during the months of April and May than any other month (P<0.001). When patients were grouped seasonally, there was a significant increase of EoE cases in spring and summer months (n=28) when compared with the fall and winter months (n=13) (P=0.019). Analysis of the second cohort of cases (n=37) from 2002 to 2006 confirmed a similar seasonal diagnostic pattern for EoE during the outdoor seasons.
Our data demonstrate that EoE has a seasonal prevalence in adults. The seasonal variation pattern found in newly diagnosed EoE cases in adults supports the potential role of aeroallergens in the pathogenesis of EoE.
A series of low-loaded metallic-activated carbon catalysts were evaluated during the selective hydrogenation of a medium-chain alkyne under mild conditions. The catalysts and support were ...characterized by ICP, hydrogen chemisorption, Raman spectroscopy, temperature-programmed desorption (TPD), temperature-programmed reduction (TPR), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR micro-ATR), transmission electronic microscopy (TEM), and X-ray photoelectronic spectroscopy (XPS). When studying the effect of the metallic phase, the catalysts were active and selective to the alkene synthesis. NiCl/C was the most active and selective catalytic system. Besides, when the precursor salt was evaluated, PdN/C was more active and selective than PdCl/C. Meanwhile, alkyne is present in the reaction media, and geometrical and electronic effects favor alkene desorption and so avoid their overhydrogenation to the alkane. Under mild conditions, nickel catalysts are considerably more active and selective than the Lindlar catalyst.
Trazpiroben is a dopamine D2/D3 receptor antagonist under development for the treatment of gastroparesis. This phase I, open‐label, randomized, two‐way crossover study (NCT04121078) evaluated the ...effect of single‐dose intravenous rifampin, a potent inhibitor of the organic anion transporting polypeptides (OATPs) 1B1 and 1B3, on the pharmacokinetics and safety of trazpiroben in healthy adults. The utility of coproporphyrin (CP) I and CPIII as biomarkers of OATP inhibition was also assessed. Overall, 12 participants were enrolled and randomized (1:1) into one of two treatment sequences (AB and BA). Participants received either a single oral dose of trazpiroben 25 mg (treatment A) or a single oral dose of trazpiroben 25 mg immediately after a single 30‐min intravenous infusion of rifampin 600 mg (treatment B). After a washout period of at least 7 days, participants received the other treatment. Geometric mean area under the curve from time 0 extrapolated to infinity (AUC∞) and maximum serum concentration (Cmax) of plasma trazpiroben were higher in participants receiving treatment B than those receiving treatment A (AUC∞, 168.5 vs. 32.68 ng*h/ml; Cmax, 89.62 vs. 14.37 ng/ml); corresponding geometric mean ratios (90% confidence interval) showed 5.16 (4.25–6.25) and 6.24 (4.62–8.42)‐fold increases in these parameters, respectively. In this study, trazpiroben was confirmed as a substrate of OATP1B1/1B3, and therefore co‐administration of trazpiroben with moderate to strong inhibitors of OATP1B1/1B3 is not recommended. This is also the first assessment of the utility of CPI and CPIII as endogenous biomarkers of OATP1B1/1B3 inhibition after a single intravenous dose of rifampin.
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