Evaluation of a six-probe cocktail (caffeine, tolbutamide, omeprazole, dextromethorphan, midazolam, and digoxin) approach to estimate hepatic drug detoxification capability and dosage requirements after a single oral dosing in healthy Chinese volunteers.

The primary objectives of this study were to investigate the suitability of a 6-probe cocktail (caffeine, tolbutamide, omeprazole, dextromethorphan, midazolam, and digoxin) to be used as a tool for assessing the activity of drug metabolizing enzymes and transporters, and examine differences in the way drugs are handled among groups with different genetic regulation of these processes. This was a single-center, open-label, phase I clinical study involving 20 young, healthy Chinese volunteers (equal gender distribution). The subjects were administered a single, oral dose of the 6-probe cocktail and serum samples were collected to assess the disposition of the different probe substrates and produced metabolites. The serum samples were analyzed using ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry technology. The DNA samples were subjected to whole exome sequencing. Nineteen healthy volunteers completed the study. The 6-probe cocktail was safe and well-tolerated by all the subjects. The parent substrates and metabolites-caffeine (paraxanthine), dextromethorphan (dextrorphan), digoxin, midazolam (1-hydroxy-midazolam), omeprazole (5-hydroxy-omeprazole), and tolbutamide (4-hydroxy-tolbutamide)-were within the detectable window. Genetic variations known to alter drug metabolism (CYP2D6*10, CYP2C19*2, CYP2C19*3, and CYP2C9*3) were identified and generally correlated with phenotypic status. The 6-probe cocktail appeared to be suitable for assessing drug metabolizing activities. This, in conjunction with individual genetics, will pave the way for the implementation of personalized medicine in clinical practice. This will hopefully improve efficacy and reduce the incidence of adverse drug reactions.

A prospective randomized study of colonoscopy using blue laser imaging and white light imaging in detection and differentiation of colonic polyps.

Background and study aims Published data on blue laser imaging (BLI) for detection and differentiation of colonic polyps are limited compared to narrow band imaging (NBI). This study investigated whether BLI can increase the detection rate of colonic polyps and adenomas when compared to white light imaging (WLI), and examined use of NICE (NBI International Colorectal Endoscopic) and JNET (Japan NBI Expert Team) classifications with BLI. Patients and methods Patients aged 50 years and above referred for colonoscopy were randomized to BLI or WLI on withdrawal. Detected polyps were characterized using NICE and JNET classifications under BLI mode and correlated with histology. Primary outcome was adenoma detection rate. Secondary outcomes were utility of NICE and JNET classifications to predict histology using BLI. Results A total of 182 patients were randomized to BLI (92) or WLI (90). Comparing BLI with WLI, the polyp detection rate was 59.8 % vs 40.0 %, P  = 0.008, and the adenoma detection rate was 46.2 % vs 27.8 %, P  = 0.010. NICE 1 and JNET 1 diagnosed hyperplastic polyps with sensitivity of 87.18 % and specificity of 84.35 %. NICE 2 diagnosed low- (LGD) or high-grade dysplasia (HGD) with sensitivity of 92.31 % and specificity of 77.45 %. JNET 2A diagnosed LGD with sensitivity of 91.95 %, and specificity of 74.53 %. Four cases of focal HGD all had JNET 2A morphology. Conclusion BLI increased adenoma detection rate compared to WLI. NICE and JNET classifications can be applied when using BLI for endoscopic diagnosis of HP and LGD but histological confirmation remains crucial.

Effects of proton pump inhibitor on the human gut microbiome profile in multi-ethnic groups in Singapore.

INTRODUCTION: The objectives of this study were to examine the effects of ethnicity, gender and a proton pump inhibitor (PPI), omeprazole, on the human gut microbiome. PPIs are commonly used for the treatment of acid-related disorders. We hypothesised that PPI therapy might perturb microbial communities and alter the gut microbiome. METHODS: Healthy subjects of Chinese (n = 12), Malay (n = 12) and Indian (n = 10) ancestry, aged 21-37 years, were enrolled. They provided a baseline stool sample (Day 1) and were then given a course of omeprazole at therapeutic dose (20 mg daily) for seven days. Stool samples were collected again on Day 7 and 14 (one week after stopping omeprazole). Microbial DNA was extracted from the stool samples, followed by polymerase chain reaction, library construction, 16S rRNA sequencing using Illumina MiSeq, and statistical and bioinformatics analyses. RESULTS: The findings showed an increase in species richness (p = 0.018) after omeprazole consumption on Day 7, which reverted to baseline on Day 14. There were significant increases in the relative abundance of Streptococcus vestibularis (p = 0.0001) and Veillonella dispar (p = 0.0001) on Day 7, which diminished on Day 14. Faecalibacterium prausnitzii, Sutterella stercoricanis and Bacteroides denticanum were characteristic of Chinese, Malays and Indians, respectively. Lactobacillaceae and Bacteroides xylanisolvens were the signature taxa of male and female subjects, respectively. CONCLUSION: The study demonstrated alterations in the gut microbiome following omeprazole treatment. This may explain the underlying pathology of increased risk of Clostridium difficile infections associated with omeprazole therapy.

Efficacy of small-volume simethicone given at least 30 min before gastroscopy.

AIM: To evaluate the efficacy of 5 mL simethicone solution in decreasing gastric foam if given at least 30 min before gastroscopy. METHODS: This was a randomized, placebo controlled, endoscopist blinded study performed at Changi General Hospital. Patients were at least 21 years old, had no prior surgical resection of the upper gastrointestinal tract, and scheduled for elective diagnostic gastroscopies. The primary outcome was the total mucosal visibility score (TMVS) which was evaluated using McNally score. The sample size was calculated to be 24 per group (SD 2.4, 80% power, P < 0.05, 2-sample t test). RESULTS: Fifty-four patients were randomised to receive either simethicone [1 mL liquid simethicone (100 mg) in 5 mL of water] or placebo (5 mL of water) at least 30 min before their gastroscopy. Six accredited consultants conducted the gastroscopy, and the interobserver agreement of scoring TMVS was good with a Kappa statistic of 0.73. The simethicone group had significantly better mean TMVS compared to placebo (5.78 ± SD 1.65 vs 8.89 ± SD 1.97, P < 0.001). The improvement was statistically significant for the duodenum and the gastric antrum, angularis, body, and fundus. Percent 51.9 of patients in the simethicone group had a TMVS of 4 (no bubbles at all) to 5 (only 1 area with minimal bubbles), while in the placebo group 3.7% of patients had TMVS of 4 or 5. The number needed to treat was 2.1 to avoid a TMVS of 6 and more. The simethicone group also had a significantly shorter procedure time with less volume of additional flushes required during gastroscopy to clear away obscuring gastric foam. CONCLUSION: With a premedication time of at least 30 min, 5 mL simethicone can significantly decrease gastric foam, decrease the volume of additional flushes, and shorten gastroscopy time.

A multicenter randomized comparison between high-definition white light endoscopy and narrow band imaging for detection of gastric lesions.

OBJECTIVE: Narrow band imaging (NBI) is generally considered to be useful for lesion characterization, but not enhanced detection of gastric lesions, because of the dark endoscopic view. We tested whether the new generation of NBI (190-NBI or 290-NBI), which is twice as bright as the previous version, would improve detection of premalignant gastric lesions compared with high-definition white light endoscopy (HD-WLE). PATIENTS AND METHODS: This was a multicenter prospective randomized study involving five tertiary institutions in the Asia-Pacific region. A total of 579 patients aged older than 50 years who underwent diagnostic upper gastrointestinal endoscopy were randomized to either HD-WLE or NBI. The outcome measurements were detection of intestinal metaplasia (IM), focal gastric lesions, and gastric cancers. RESULTS: Focal gastric lesions were detected in 83/286 (29%) and 119/293 patients (40.6%) by HD-WLE and by NBI, respectively (P=0.003). IM was detected in 22/286 patients (7.7%) by HD-WLE and in 52/293 patients (17.7%) by NBI (P<0.001). Gastric cancer were found in 7/286 (2.4%) and 3/293 patients (1%) in HD-WLE and NBI groups, respectively (P=0.189). CONCLUSION: NBI increased the detection rate of IM compared with HD-WLE.