Management of laryngopharyngeal reflux with proton pump inhibitors

There is a lack of consistent guidelines and consensus for the diagnosis of laryngopharyngeal reflux (LPR). A therapeutic trial with a proton pump inhibitor (PPI) has been suggested to identify patients with LPR. This review focuses on the current difficulties in diagnosing the disease and examines the evidence for the effectiveness of PPI therapy in suspected reflux-related laryngeal symptoms. Additionally, mode of action, safety, and tolerability of PPIs are described. A total of 7 placebo-controlled trials were identified and included in the review. All studies evaluated the effect of a PPI on symptoms and objective laryngoscopic findings in suspected LPR. Data from these trials show that PPI therapy is no more effective than placebo in producing symptom relief in patients suspected of LPR. Symptoms, laryngoscopic findings, or abnormal findings on pH monitoring will not predict response to PPI therapy. High placebo response levels suggest a much more complex and multifactorial pathophysiology of LPR than simple acid reflux. Further studies are needed to characterize subgroups of patients with reflux-associated laryngeal symptoms that might benefit from treatment with PPI. Future studies should use validated patient reported outcome measures with endpoints that represent a predefined clinically meaningful change in symptom scores

Oral supplementation of healthy adults with 2'-O-fucosyllactose and lacto-N-neotetraose is well tolerated and shifts the intestinal microbiota

The gut microbiota has been established as an important player influencing many aspects of human physiology. Breast milk, the first diet for an infant, contains human milk oligosaccharides (HMO) that shape the infant's gut microbiota by selectively stimulating the growth of specific bacteria, especially bifidobacteria. In addition to their bifidogenic activity, the ability of HMO to modulate immune function and the gut barrier makes them prime candidates to restore a beneficial microbiota in dysbiotic adults and provide health benefits. We conducted a parallel, double-blind, randomised, placebo-controlled, HMO-supplementation study in 100 healthy, adult volunteers, consuming chemically produced 2'-O-fucosyllactose (2'FL) and/or lacto-N-neotetraose (LNnT) at various daily doses and mixes or placebo for 2 weeks. All participants completed the study without premature discontinuation. Supplementation of 2'FL and LNnT at daily doses up to 20 g was shown to be safe and well tolerated, as assessed using the gastrointestinal symptoms rating scale. 16S rRNA sequencing analysis showed that HMO supplementation specifically modified the adult gut microbiota with the primary impact being substantial increases in relative abundance of Actinobacteria and Bifidobacterium in particular and a reduction in relative abundance of Firmicutes and Proteobacteria. This study provides the first set of data on safety, tolerance and impact of HMO on the adult gut microbiota. Collectively, the results from this study show that supplementing the diet with HMO is a valuable strategy to shape the human gut microbiota and specifically promote the growth of beneficial bifidobacteria

Initial validation of a diagnostic questionnaire for gastroesophageal reflux disease

Brief, reliable, and valid self-administered questionnaires could facilitate the diagnosis of gastroesophageal reflux disease in primary care. We report the development and validation of such an instrument. Methods Content validity was informed by literature review, expert opinion, and cognitive interviewing of 50 patients resulting in a 22-item survey. For psychometric analyses, primary care patients completed the new questionnaire at enrollment and at intervals ranging from 3 days to 3 wk. Multitrait scaling, test–retest reliability, and responsiveness were assessed. Predictive validity analyses of all scales and items used specialty physician diagnosis as the “gold standard.” Results Iterative factor analyses yielded three scales of four items each including heartburn, acid regurgitation, and dyspepsia. Multitrait scaling criteria including internal consistency, item interval consistency, and item discrimination were 100% satisfied. Test–retest reliability was high in those reporting stable symptoms. Scale scores significantly changed in those reporting a global change. Regressing specialty physician diagnosis on the three scales revealed significant effects for two scales (heartburn and regurgitation). Combining the two significant scales enhanced the strength of the model. Symptom response to self-directed treatment with nonprescription antisecretory medications was highly predictive of the diagnosis also, although the item demonstrated poor validity and reliability. Conclusions A brief, simple 12-item questionnaire demonstrated validity and reliability and seemed to be responsive to change for reflux and dyspeptic symptoms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72526/1/j.1572-0241.2001.03451.x.pd

Mining, analyzing, and integrating viral signals from metagenomic data

Abstract Background Viruses are important components of microbial communities modulating community structure and function; however, only a couple of tools are currently available for phage identification and analysis from metagenomic sequencing data. Here we employed the random forest algorithm to develop VirMiner, a web-based phage contig prediction tool especially sensitive for high-abundances phage contigs, trained and validated by paired metagenomic and phagenomic sequencing data from the human gut flora. Results VirMiner achieved 41.06% ± 17.51% sensitivity and 81.91% ± 4.04% specificity in the prediction of phage contigs. In particular, for the high-abundance phage contigs, VirMiner outperformed other tools (VirFinder and VirSorter) with much higher sensitivity (65.23% ± 16.94%) than VirFinder (34.63% ± 17.96%) and VirSorter (18.75% ± 15.23%) at almost the same specificity. Moreover, VirMiner provides the most comprehensive phage analysis pipeline which is comprised of metagenomic raw reads processing, functional annotation, phage contig identification, and phage-host relationship prediction (CRISPR-spacer recognition) and supports two-group comparison when the input (metagenomic sequence data) includes different conditions (e.g., case and control). Application of VirMiner to an independent cohort of human gut metagenomes obtained from individuals treated with antibiotics revealed that 122 KEGG orthology and 118 Pfam groups had significantly differential abundance in the pre-treatment samples compared to samples at the end of antibiotic administration, including clustered regularly interspaced short palindromic repeats (CRISPR), multidrug resistance, and protein transport. The VirMiner webserver is available at http://sbb.hku.hk/VirMiner/. Conclusions We developed a comprehensive tool for phage prediction and analysis for metagenomic samples. Compared to VirSorter and VirFinder—the most widely used tools—VirMiner is able to capture more high-abundance phage contigs which could play key roles in infecting bacteria and modulating microbial community dynamics. Trial registration The European Union Clinical Trials Register, EudraCT Number: 2013-003378-28. Registered on 9 April 201