Virological and Serological Assessment of US Army Trainees Isolated for Coronavirus Disease 2019.

BACKGROUND: Laboratory screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key mitigation measure to avoid the spread of infection among recruits starting basic combat training in a congregate setting. Because viral nucleic acid can be detected persistently after recovery, we evaluated other laboratory markers to distinguish recruits who could proceed with training from those who were infected. METHODS: Recruits isolated for coronavirus disease 2019 (COVID-19) were serially tested for SARS-CoV-2 subgenomic ribonucleic acid (sgRNA), and viral load (VL) by reverse-transcriptase polymerase chain reaction (RT-PCR), and for anti- SARS-CoV-2. Cluster and quadratic discriminant analyses of results were performed. RESULTS: Among 229 recruits isolated for COVID-19, those with a RT-PCR cycle threshold >30.49 (sensitivity 95%, specificity 96%) or having sgRNA log10 RNA copies/mL <3.09 (sensitivity and specificity 96%) at entry into isolation were likely SARS-CoV-2 uninfected. Viral load >4.58 log10 RNA copies/mL or anti-SARS-CoV-2 signal-to-cutoff ratio <1.38 (VL: sensitivity and specificity 93%; anti-SARS-CoV-2: sensitivity 83%, specificity 79%) had comparatively lower sensitivity and specificity when used alone for discrimination of infected from uninfected. CONCLUSIONS: Orthogonal laboratory assays used in combination with RT-PCR may have utility in determining SARS-CoV-2 infection status for decisions regarding isolation.

A Randomized Pilot Study to Compare the Effectiveness of a Low FODMAP Diet vs Psyllium in Patients With Fecal Incontinence and Loose Stools.

INTRODUCTION: The aim of the study was to compare the effectiveness of a low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet (LFD) vs psyllium on the frequency and severity of fecal incontinence (FI) episodes in patients with loose stools. METHODS: This was a single-center, randomized pilot trial of adult patients with FI (Rome III) with at least 1 weekly FI episode associated with loose stool. Eligible patients were randomized to 4 weeks of either a dietitian-led LFD or 6 g/d psyllium treatment. RESULTS: Forty-three subjects were randomized from October 2014 to May 2019. Thirty-seven patients completed the study (19 LFD and 18 psyllium). There was no statistically significant difference in the proportion of treatment responders (>50% reduction in FI episodes compared with baseline) for treatment weeks 1-4 (LFD 38.9%, psyllium 50%, P = .33). Compared with baseline, mean fecal incontinence severity index score significantly improved with LFD (39.4 vs 32.6, P = .02) but not with psyllium (35.4 vs 32.1, P = .29). Compared with baseline values, the LFD group reported improvements in fecal incontinence quality of life coping/behavior, depression/self-perception, and embarrassment subscales. The psyllium group reported improvement in incontinence quality of life coping/behavior. DISCUSSION: In this pilot study, there was no difference in the proportion of patients who reported a 50% reduction of FI episodes with the LFD or psyllium. Subjects in the psyllium group reported a greater reduction in overall FI episodes, whereas the LFD group reported consistent improvements in FI severity and quality of life. Further work to understand these apparently discrepant results are warranted but the LFD and psyllium seem to provide viable treatment options for patients with FI and loose stools.

Serological and RT-PCR Surveillance for COVID-19 in an Asymptomatic US Army Trainee Population.

BACKGROUND: Significant variability exists in the application of infection control policy throughout the US Army initial entry training environment. To generate actionable information for the prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/coronavirus disease 2019 (COVID-19) transmission among new recruits, active enhanced surveillance was conducted for evidence of and exposure to SARS-CoV-2/COVID-19. METHODS: We serially tested recruits with a reverse transcriptase polymerase chain reaction (RT-PCR) COVID-19 and/or total antibody to SARS-CoV-2 tests at days 0, 14, and week 10 upon arrival for basic combat training at a location in the Southern United States. RESULTS: Among 1403 recruits who were enrolled over a 6-week period from August 25 through October 11, 2020, 84 recruits tested positive by RT-PCR, with more than half (55%, 46/84) testing positive at arrival and almost two-thirds (63%, 53/84) also testing seropositive at arrival. Similarly, among an overall 146 recruits who tested seropositive for SARS-CoV-2 during the period of observation, a majority (86%) tested seropositive at arrival; no hospitalizations were observed among seropositive recruits, and antibody response increased at week 10. CONCLUSIONS: These findings that suggest serological testing may complement current test-based measures and provide another tool to incorporate in COVID-19 mitigation measures among trainees in the US Army.

Exploratory Comparative Effectiveness Trial of Green Kiwifruit, Psyllium, or Prunes in US Patients With Chronic Constipation.

INTRODUCTION: Psyllium and prunes are proven treatments for chronic constipation (CC). Asian studies suggest that kiwifruit may also benefit CC symptoms. We report a partially randomized, comparative effectiveness trial evaluating kiwifruit, psyllium, and prunes in US patients with CC. METHODS: Adults with CC at a US medical center were randomized to 3 natural treatments. Eligible patients had ≤3 complete spontaneous bowel movements (CSBMs) per week and were partially randomized to green kiwifruit (2/d), prunes (100 g/d), or psyllium (12 g/d) for 4 weeks. The primary endpoint was the proportion of patients in each group reporting an increase of ≥1 CSBM per week compared with baseline for at least 2 of 4 treatment weeks. Key secondary outcomes included stool frequency, stool consistency, and straining assessed daily. Treatment satisfaction and adverse events (AEs) were also measured. Standard statistical methods were used, and a P < 0.05 was considered significant. RESULTS: Seventy-nine patients with CC (mean age = 42.7 years, 87% female, and 77% white) were partially randomized. Complete data were available for 75 patients (kiwifruit 29, prunes 24, and psyllium 22). For the primary endpoint, proportions of CSBM responders were similar for the treatments. For secondary outcomes comparing treatment weeks 3 and 4 to baseline, there was a significant increase in weekly CSBM rate with all 3 treatments (P ≤ 0.003); stool consistency significantly improved with kiwifruit (P = 0.01) and prunes (P = 0.049); and straining significantly improved with kiwifruit (P = 0.003), prunes (P < 0.001), and psyllium (P = 0.04). Patients randomized to the kiwifruit group reported significant improvement in bloating scores (P = 0.02). AEs were most common with psyllium and least common with kiwifruit. At the end of treatment, a smaller proportion of patients were dissatisfied with kiwifruit compared with prunes or psyllium (P = 0.02). DISCUSSION: Kiwifruit, prunes, and psyllium improve constipation symptoms in patients with CC. Kiwifruit was associated with the lowest rate of AEs and dissatisfaction with therapy.

Evidence of Duodenal Epithelial Barrier Impairment and Increased Pyroptosis in Patients With Functional Dyspepsia on Confocal Laser Endomicroscopy and "Ex Vivo" Mucosa Analysis.

INTRODUCTION: Duodenal epithelial barrier impairment and immune activation may play a role in the pathogenesis of functional dyspepsia (FD). This study was aimed to evaluate the duodenal epithelium of patients with FD and healthy individuals for detectable microscopic structural abnormalities. METHODS: This is a prospective study using esophagogastroduodenoscopy enhanced with duodenal confocal laser endomicroscopy (CLE) and mucosal biopsies in patients with FD (n = 16) and healthy controls (n = 18). Blinded CLE images analysis evaluated the density of epithelial gaps (cell extrusion zones), a validated endoscopic measure of the intestinal barrier status. Analyses of the biopsied duodenal mucosa included standard histology, quantification of mucosal immune cells/cytokines, and immunohistochemistry for inflammatory epithelial cell death called pyroptosis. Transepithelial electrical resistance (TEER) was measured using Ussing chambers. Epithelial cell-to-cell adhesion proteins expression was assessed by real-time polymerase chain reaction. RESULTS: Patients with FD had significantly higher epithelial gap density on CLE in the distal duodenum than that of controls (P = 0.002). These mucosal abnormalities corresponded to significant changes in the duodenal biopsy samples of patients with FD, compared with controls, including impaired mucosal integrity by TEER (P = 0.009) and increased number of epithelial cells undergoing pyroptosis (P = 0.04). Reduced TEER inversely correlated with the severity of certain dyspeptic symptoms. Furthermore, patients with FD demonstrated altered duodenal expression of claudin-1 and interleukin-6. No differences in standard histology were found between the groups. DISCUSSION: This is the first report of duodenal CLE abnormalities in patients with FD, corroborated by biopsy findings of epithelial barrier impairment and increased cell death, implicating that duodenal barrier disruption is a pathogenesis factor in FD and introducing CLE a potential diagnostic biomarker in FD.

The Impact of a 4-Week Low-FODMAP and mNICE Diet on Nutrient Intake in a Sample of US Adults with Irritable Bowel Syndrome with Diarrhea.

BACKGROUND: A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) has gained increasing acceptance for the treatment of irritable bowel syndrome but safety concerns have been raised regarding nutritional adequacy. Changes in nutrient intake during the elimination phase of the low-FODMAP diet remain predominantly unknown. OBJECTIVE: To determine changes in the mean reported daily nutrient content before and after 4 weeks of a low-FODMAP diet vs modified National Institute for Health and Clinical Excellence (mNICE) dietary intervention and to identify nutritional inadequacies based on comparison to the Dietary Reference Intakes in patients with irritable bowel syndrome-diarrhea subtype. DESIGN: Post hoc analysis of a randomized controlled trial entailing a 4-week trial period comparing the low-FODMAP and mNICE diets. PARTICIPANTS AND SETTING: A total of 78 patients (41 low FODMAP and 37 mNICE) meeting the Rome III criteria for irritable bowel syndrome-diarrhea subtype were consecutively recruited from gastroenterology and primary care clinics at the University of Michigan Medical Center between October 2012 and November 2015. METHODS: Participants randomized to the low-FODMAP arm were instructed to decrease their dietary intake of FODMAPs, whereas participants randomized to the mNICE intervention arm were instructed to eat small frequent meals, avoid trigger foods, and avoid excess alcohol and caffeine. MAIN OUTCOME MEASURES: Post hoc evaluation for presence of micronutrient deficiencies per Dietary Reference Intakes when implementing low-FODMAP vs mNICE dietary interventions. Dietary intake was analyzed via 3-day food diaries at baseline and during the final week of the assigned diet. STATISTICAL ANALYSES PERFORMED: A post hoc analysis utilizing either a t test or χ2 analysis was conducted between before and after data. RESULTS: Both diets resulted in fewer daily kilocalories consumed, fewer number of daily meals consumed, and less daily carbohydrate intake. Among the patients following the low-FODMAP diet, there was a statistically significant decrease from baseline in several micronutrients, which was not observed in the mNICE cohort. However, these differences in the low-FODMAP group remained significant only for riboflavin after correcting for calorie-adjusted nutrient intake. Comparing Dietary Reference Intakes of participants pre- and postintervention, fewer patients met the Dietary Reference Intakes for thiamin and iron in the low FODMAP group, and for calcium and copper in the mNICE group. CONCLUSIONS: During a 4-week dietary intervention, the mean daily intake of most micronutrients remained stable and within the Recommended Dietary Allowances for both diets. Although decrease in several micronutrients was observed with implementation of the low-FODMAP diet relative to the mNICE diet, most of these disappeared after adjusting for energy intake.

Factors Associated with Surveillance Adenoma and Sessile Serrated Polyp Detection Rates.

BACKGROUND: Adenoma detection rate (ADR) and sessile serrated polyp detection rate (SSPDR) data in surveillance colonoscopy are limited. AIMS: Our aim was to determine surveillance ADR and SSPDR and identify associated predictors. METHODS: A retrospective review of subjects who underwent surveillance colonoscopy for adenoma and/or SSP at an academic center was performed. The following exclusion criteria were applied: prior colonoscopy ≤ 3 years, incomplete examination, or another indication for colonoscopy. Patient, endoscopist, and procedure characteristics were collected. Predictors were identified using multivariable logistic regression. RESULTS: Of 3807 colonoscopies, 2416 met inclusion criteria. Surveillance ADR was 49% and, SSPDR was 8%. Higher ADR was associated with: age per year (OR 1.03; 95% CI 1.02-1.04), male gender (OR 1.55; 95% CI 1.29-1.88), BMI per kg/m2 (OR 1.02; 95% CI 1.01-1.04), withdrawal time per minute (OR 1.09; 95% CI 1.07-1.10), and endoscopists' screening ADR (OR 1.01; 95% CI 1.00-1.03). Years since training (OR 0.99; 95% CI 0.98-0.99) was associated with lower ADR. Family history of CRC (OR 1.58; 95% CI 1.02-2.27) and endoscopists' screening ADR (OR 1.40; 95% CI 1.15-1.74) were associated with higher SSPDR. African-American race (OR 0.36; 95% CI 0.10-0.75) and diabetes (OR 0.41; 95% CI 0.21-0.76) were associated with lower SSPDR. CONCLUSIONS: For surveillance colonoscopy, nearly half of patients had an adenoma and one in twelve had an SSP. In addition to established factors, BMI, endoscopists' screening ADR, and years since training were associated with ADR, whereas African-American race and diabetes were inversely associated with SSPDR. Further studies are needed prior to integrating surveillance ADR and SSPDR into quality metrics.

A Diet Low in Fermentable Oligo-, Di-, and Monosaccharides and Polyols Improves Quality of Life and Reduces Activity Impairment in Patients With Irritable Bowel Syndrome and Diarrhea.

BACKGROUND & AIMS: We investigated the effects of a diet low in fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) vs traditional dietary recommendations on health-related quality of life (QOL), anxiety and depression, work productivity, and sleep quality in patients with irritable bowel syndrome and diarrhea (IBS-D). METHODS: We conducted a prospective, single-center, single-blind trial of 92 adult patients with IBS-D (65 women; median age, 42.6 years) randomly assigned to groups placed on a diet low in FODMAPs or a modified diet recommended by the National Institute for Health and Care Excellence (mNICE) for 4 weeks. IBS-associated QOL (IBS-QOL), psychosocial distress (based on the Hospital Anxiety and Depression Scale), work productivity (based on the Work Productivity and Activity Impairment), and sleep quality were assessed before and after diet periods. RESULTS: Eighty-four patients completed the study (45 in the low-FODMAP group and 39 in the mNICE group). At 4 weeks, patients on the diet low in FODMAPs had a larger mean increase in IBS-QOL score than did patients on the mNICE diet (15.0 vs 5.0; 95% CI, -17.4 to -4.3). A significantly higher proportion of patients in the low-FODMAP diet group had a meaningful clinical response, based on IBS-QOL score, than in the mNICE group (52% vs 21%; 95% CI, -0.52 to -0.08). Anxiety scores decreased in the low-FODMAP diet group compared with the mNICE group (95% CI, 0.46-2.80). Activity impairment was significantly reduced with the low-FODMAP diet (-22.89) compared with the mNICE diet (-9.44; 95% CI, 2.72-24.20). CONCLUSIONS: In a randomized, controlled trial, a diet low in FODMAPs led to significantly greater improvements in health-related QOL, anxiety, and activity impairment compared with a diet based on traditional recommendations for patients with IBS-D. ClinicalTrials.gov, number NCT01624610.

A Randomized Controlled Trial Comparing the Low FODMAP Diet vs. Modified NICE Guidelines in US Adults with IBS-D.

OBJECTIVES: There has been an increasing interest in the role of fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) in irritable bowel syndrome (IBS). We report results from the first randomized controlled trial of the low FODMAP diet in US adults with IBS and diarrhea (IBS-D). The objectives were to compare the efficacy of the low FODMAP diet vs. a diet based upon modified National Institute for Health and Care Excellence guidelines (mNICE) on overall and individual symptoms in IBS-D patients. METHODS: This was a single-center, randomized-controlled trial of adult patients with IBS-D (Rome III) which compared 2 diet interventions. After a 2-week screening period, eligible patients were randomized to a low FODMAP or mNICE diet for 4 weeks. The primary end point was the proportion of patients reporting adequate relief of IBS-D symptoms ≥50% of intervention weeks 3-4. Secondary outcomes included a composite end point which required response in both abdominal pain (≥30% reduction in mean daily pain score compared with baseline) and stool consistency (decrease in mean daily Bristol Stool Form of ≥1 compared with baseline), abdominal pain and stool consistency responders, and other key individual IBS symptoms assessed using daily questionnaires. RESULTS: After screening, 92 subjects (65 women, median age 42.6 years) were randomized. Eighty-four patients completed the study (45 low FODMAP, 39 mNICE). Baseline demographics, symptom severity, and nutrient intake were similar between groups. Fifty-two percent of the low FODMAP vs. 41% of the mNICE group reported adequate relief of their IBS-D symptoms (P=0.31). Though there was no significant difference in the proportion of composite end point responders (P=0.13), the low FODMAP diet resulted in a higher proportion of abdominal pain responders compared with the mNICE group (51% vs. 23%, P=0.008). Compared with baseline scores, the low FODMAP diet led to greater reductions in average daily scores of abdominal pain, bloating, consistency, frequency, and urgency than the mNICE diet. CONCLUSIONS: In this US trial, 40-50% of patients reported adequate relief of their IBS-D symptoms with the low FODMAP diet or a diet based on modified NICE guidelines. The low FODMAP diet led to significantly greater improvement in individual IBS symptoms, particularly pain and bloating, compared with the mNICE diet.