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SUMMARY BackgroundThe direct and indirect costs of sedation limit access to screening colonoscopy amongst United States veterans.

Background The relationship between gut microbial community composition at the higher-taxonomic order-level and local and systemic immunologic abnormalities in HIV disease may provide insight into how bacterial translocation impacts HIV disease. Methods Antiretroviral (ART)-naive HIV patients underwent upper endoscopy before and nine months after starting ART. Duodenal tissue was paraffin-embedded for immunohistochemical analysis (IHC) and digested for FACS for T-cell subsets and immune activation (CD38+/HLA-DR+) enumeration. Stool samples were provided from patients and controls for comparison. Metagenomic microbial DNA was extracted from feces for optimized 16S ribosomal RNA gene (rDNA) real-time qPCR assays designed to quantify panbacterial loads and the relative abundances of proinflammatory Enterobacteriales order, and the dominant Bacteroidales and Clostridiales orders. Results Samples from 10 HIV-subjects prior to initiating, and from 6 subjects receiving, ART were available for analysis. There was a trend for a greater proportion of Enterobacteriales in HIV-positive subjects compared to controls (p=0.099). There were significant negative correlations between total bacterial load and duodenal CD4+ and CD8+ T-cell activation levels (r= −0.74, p= 0.004 and r= −0.67, p=0.013, respectively). The proportions of Enterobacteriales and Bacteroidales were significantly correlated with duodenal CD4+ T-cell depletion and peripheral CD8+ T-cell activation, respectively. Conclusions These data represent the first report of quantitative molecular and cellular correlations between total/universal and order-level gut bacterial populations and GALT levels of immune activation in HIV-infected subjects. The correlations between lower overall 16S rDNA levels and tissue immune activation suggest that the gut microbiome may contribute to immune activation and influence HIV progression.

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Failure of cecal intubation when using air insufflation during scheduled unsedated colonoscopy in veterans prompted a literature search for a less uncomfortable approach. Water-related maneuvers as "adjuncts" to air insufflation were identified as effective in minimizing discomfort, although medication requirement was not reduced and willingness to repeat unsedated colonoscopy was not addressed. These adjunct maneuvers were combined with turning the air pump off to avoid colon elongation during insertion. Warm water infusion in lieu of air insufflation was evaluated in observational studies. Subsequent refinements evolved into the water method - a combination of air exclusion by aspiration of residual air to minimize angulations at flexures and a dynamic process of water exchange to remove feces in order to clear the view and aid insertion. In subsequent randomized controlled trials, the water method significantly reduced medication requirement, increased the proportion of patients in whom complete unsedated colonoscopy could be achieved, reduced patient recovery time burdens (sedation on demand), decreased abdominal discomfort during and after colonoscopy, enhanced cecal intubation, and increased willingness to repeat the procedure (scheduled unsedated). Supervised education of trainees and self-learning by an experienced colonoscopist were feasible. Lessons learned in developing the water method for optimizing patient-centered outcomes are presented. These proof-of-principle observations merit further research assessment in diverse settings.

One study in sedated patients demonstrated a reduction in pain score but not midazolam dosage when warm water infusion was used to manage colonic spasm. We describe pilot data with a modified warm water infusion technique. We tested the hypothesis that patients receiving even only half of the usual dose of sedation medications would have acceptable cecal intubation and tolerate the procedure well, based on retrospective review of prospectively collected data from a single Veterans Affairs (VA) medical center. Group 1 included 32 consecutive patients who received full-dose and group 2 included 43 consecutive patients who received half-dose premedication. Insertion of colonoscope was aided by warm water infusion in lieu of air insufflation. Pain scores during insertion, cecal intubation rate, and total amount of medications were monitored. The novel technique permitted equal cecal intubation rate at reduced total dose of medications. Pain scores were not significantly different. The uncontrolled nonrandomized observational nature of the data is one limitation. The nonsignificant difference in pain scores may be affected by a type II error. These pilot data suggest that insertion is feasible without air when water infusion is used. The novel technique may be a useful adjunct for minimizing the dosage of sedation medications without adversely affecting cecal intubation. Further study is needed to compare air insufflation and water infusion with regard to patient tolerance and success, particularly in the presence of an on-demand sedation policy.